Tissue Disease Species symbol ID Platform Type Expression Target Pathway Method Drug Function PMID Title Year liver liver_cirrhosis mus_musculus ctgf 100194970 Gene mRNA promoter methylation CTGF NA qRT-PCR; etc. no "Ctgf gene promoter methylation may prevent the development of hepatic fibrosis, and low level of ctgf gene promoter methylation in hscs may be a predisposing factor for developing liver fibrotic disease." 27069546 Role of CTGF gene promoter methylation in the development of hepatic fibrosis 2016 heart endomyocardial_fibrosis mus_musculus Irf1 16362 Gene mRNA sumoylation NA JAK-STAT SIGNALING PATHWAY PCR; immunofluorescence etc. no 5-azacytidine (5AZ) had a protective effect after mi by potentiation of IRF1 sumoylation and is suggested as a novel therapeutic intervention for cardiac repair. 26510961 5-Azacytidine modulates interferon regulatory factor 1 in macrophages to exert a cardioprotective effect.Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis 2015 heart endomyocardial_fibrosis rattus_norvegicus Irf1 24508 Gene mRNA sumoylation NA JAK-STAT SIGNALING PATHWAY PCR; immunofluorescence etc. no 5-azacytidine (5AZ) had a protective effect after mi by potentiation of IRF2 sumoylation and is suggested as a novel therapeutic intervention for cardiac repair. 26510961 5-Azacytidine modulates interferon regulatory factor 1 in macrophages to exert a cardioprotective effect.Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis 2015 heart cardiomegaly mus_musculus Dec 20893 Gene mRNA up-regulation FGF10 NA Masson's trichrome staining; RT-PCR; etc. no "A dec1 deficiency protects the heart from perivascular fibrosis, regulates M1/M2 macrophage polarization and reduces cell apoptosis." 32896382 "Dec1 deficiency protects the heart from fibrosis, inflammation, and myocardial cell apoptosis in a mouse model of cardiac hypertrophy" 2020 heart endomyocardial_fibrosis mus_musculus Dec 20893 Gene mRNA up-regulation FGF10 NA Masson's trichrome staining; RT-PCR; etc. no "A dec1 deficiency protects the heart from perivascular fibrosis, regulates M1/M3 macrophage polarization and reduces cell apoptosis." 32896382 "Dec1 deficiency protects the heart from fibrosis, inflammation, and myocardial cell apoptosis in a mouse model of cardiac hypertrophy" 2020 heart myocardial_infarction mus_musculus Dlk1 13386 Gene mRNA down-regulation DLK1 TGF-BETA SIGNALING PATHWAY cell proliferation assays no An inhibitory role of DLK1 of cardiac fibroblast-to-myofibroblast differentiation by interfering with TGF-beta/smad-3 signalling in the myocardium. 29668883 Deletion of delta-like 1 homologue accelerates fibroblast-myofibroblast differentiation and induces myocardial fibrosis 2019 heart myocardial_infarction mus_musculus Apln 58812 Gene mRNA down-regulation LGR4 APELIN SIGNALING PATHWAY immunofluorescence; qRT-PCR; no Apelin counterregulated against transverse aortic constriction (TAC)-mediated ascending aortic remodeling and angiotensin ii-induced promotion of cellular migration by blocking at1 receptor and miRNA-122 levels and preventing activation of the TGF-beta1-CTGF-NFAT5 and LRRF-beta-catenin signaling. 27773659 Ascending aortic adventitial remodeling and fibrosis are ameliorated with Apelin-13 in rats after TAC via suppression of the miRNA-122 and LGR4-beta-catenin signaling 2016 heart cardiomegaly mus_musculus Atf3 11910 Gene mRNA down-regulation MAP2K3 MAPK SIGNALING PATHWAY nonbiased approach; gain of function approas; CHIP no ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing MAP2K3 expression and subsequent p38-transforming growth factor-beta signaling. 28249877 Cardiac Fibroblast-Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling 2017 heart endomyocardial_fibrosis homo_sapiens RASSF1-A 11186 Gene mRNA down-regulation NA RAS SIGNALING PATHWAY NA no DNAMT3A likely plays an essential role in rassf1a mediated upregulation of erk1/2 in rat cardiac fibrosis. DNMT3A and Rassf1a may serve as a new mechanism for cardiac fibrosis. 24945829 DNMT3A silencing RASSF1A promotes cardiac fibrosis through upregulation of ERK1/2 2014 heart myocardial_infarction mus_musculus Mettl3 56335 Gene mRNA up-regulation NA TGF-BETA SIGNALING PATHWAY NA no "Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite." 33150686 Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts 2020 heart endomyocardial_fibrosis homo_sapiens RASAL1 8437 Gene mRNA methylation NA TGF-BETA SIGNALING PATHWAY qPCR; enzyme-linked immunosorbent assay etc. no "Hif1 alfa and transforming growth factor (TGF) / smad signaling pathway regulate hypoxia induced endothelial-to-mesenchymal transition (EndMT). through dnmt3a mediated rasal1 promoter hypermethylation and direct snail induction, and participate in the process of myocardial fibrosis." 27012941 Hypoxia-induced endothelial-mesenchymal transition is associated with RASAL1 promoter hypermethylation in human coronary endothelial cells. 2016 heart heart_failure homo_sapiens BMP7 655 Gene mRNA hyper-methylation NA NOTCH SIGNALING PATHWAY PCR; dual-luciferase reporter assay etc. no Highly methylated bmp-7 can block the end epithelial-mesenchymal transition (EMT) induced by TGF-beta and reduce fibrosis by regulating the activity of ve cadherin promoter. 25587097 Endocardial fibroelastosis is caused by aberrant endothelial to mesenchymal transition 2015 heart cardiomegaly homo_sapiens IGF-IIR 25151 Gene mRNA histone acetylation NA NA NA no Histone acetylation plays a critical role in IGF-iir up-regulation during pathological cardiac diseases and might provide a targeting gene in transcriptional therapies for the failing heart. 21412773 Histone acetylation is essential for ANG-II-induced IGF-IIR gene expression in H9c2 cardiomyoblast cells and pathologically hypertensive rat heart. 2013 heart myocardial_infarction mus_musculus Gpr19 14760 Gene mRNA up-regulation MTFR1 NA transferase-mediated duip nick red labelinc; etc. no Inhibition of Gpr19 improves cardiac function and reduces apoptosis and myocardial fibrosis scar formation in vivo. 31622017 Inhibition of the LncRNA Gpr19 attenuates ischemia-reperfusion injury after acute myocardial infarction by inhibiting apoptosis and oxidative stress via the miR-324-5p/Mtfr1 axis 2020 heart ventricular_dysfunction mus_musculus Kl 16591 Gene mRNA down-regulation NA TGF-BETA SIGNALING PATHWAY NA no Klotho prevents ang ii-induced cardiac remodeling and dysfunction through modifying the TGF-beta1-miR-132 axis. 31325434 "Klotho inhibits angiotensin II-induced cardiac hypertrophy, fibrosis, and dysfunction in mice through suppression of transforming growth factor-beta1 signaling pathway" 2019 heart myocardial_infarction mus_musculus Mcpip 31358 Gene mRNA down-regulation NA NF-KAPPA B SIGNALING PATHWAY NA no "Mcpip expression in the ischemic myocardium protects against adverse cardiac remodeling and dysfunction following myocardial infarction (MI) by modulation of local myocardial inflammation, possibly through mitigating NF-Kb signaling and suppressing inflammation-associated microrna expression." 25840774 MCP-1-induced protein attenuates post-infarct cardiac remodeling and dysfunction through mitigating NF-KB activation and suppressing inflammation-associated microRNA expression 2015 heart atrial_fibrillation homo_sapiens WWP-1 11059 Gene mRNA up-regulation WWP-1 TGF-BETA SIGNALING PATHWAY PCR; MTT ASSAY etc. no miR-21 inhibits cardiac fibroblasts proliferation by inactivating the TGF-beta1/smad2 signaling pathway via up-regulation of WWP1. 28495464 MicroRNA-21 via Dysregulation of WW Domain-Containing Protein 1 Regulate Atrial Fibrosis in Atrial Fibrillation 2017 heart heart_failure homo_sapiens MECP2 4204 Gene mRNA methylation NA NA CHIP; PCR etc. no miR-212/132 was upregulated after transverse aortic constriction or on activation of alfa1- and beta1-adrenoceptors and miR-212/132 led to repression of methyl-CpG-binding protein 2 (MeCP2). 26195221 Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure. 2015 heart heart_failure mus_musculus Mecp2 17257 Gene mRNA methylation NA NA CHIP; PCR etc. no miR-212/132 was upregulated after transverse aortic constriction or on activation of alfa1- and beta1-adrenoceptors and miR-212/132 led to repression of methyl-CpG-binding protein 2 (MeCP3). 26195221 Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure. 2015 heart endomyocardial_fibrosis mus_musculus Sp1 24790 Gene mRNA up-regulation SP1 TGF-BETA SIGNALING PATHWAY MTT ASSAY; PCR etc. no miR-7a/b has an anti-fibrotic role in ang ii-treated cardiac fibroblasts (CFs) that is mediated by sp1 mechanism involving the TGF-beta and MAPKs pathways. 25923922 Sp1 Mediates a Therapeutic Role of MiR-7a/b in Angiotensin II-Induced Cardiac Fibrosis via Mechanism Involving the TGF-beta and MAPKs Pathways in Cardiac Fibroblasts 2015 heart myocardial_infarction mus_musculus Trif 225471 Gene mRNA up-regulation RAAS NA Echocardiography; RT-PCR no Overexpression of cardiac micrornas (miR)-34a reversed the cardiac benefits of TRIF deficiency in aldosterone-treated mice. 32542395 TRIF/miR-34a mediates aldosterone-induced cardiac inflammation and remodeling 2020 heart myocardial_infarction homo_sapiens PFN2 5217 Gene mRNA up-regulation MIR-378;GRB2 NA dual-luciferase reporter assay no "PCFL, and the mechanism involves the direct interaction of PCFL with miR-378, which in turn relieves the inhibition effect of miR-378 on GRB2 and promotes cardiac fibrosis." 31220469 LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction 2019 heart endomyocardial_fibrosis homo_sapiens PFN2 5217 Gene mRNA up-regulation PTAFR NA immunofluorescence; qRT-PCR no Pfl/ptafr/let-7d-dependent gene regulatory mechanism proposed by the authors manifests the hypothesis of competing endogenous rnas to cardiac fibrosis. 29463987 LET's sponge: How the lncRNA PFL promotes cardiac fibrosis/LncRNA PFL contributes to cardiac fibrosis by acting as a competing endogenous RNA of let-7d 2018 heart diabetic_cardiomyopathy homo_sapiens PRPF31 26121 Gene mRNA down-regulation ZEB1 NA RT-PCR; etc. yes Rg1 inhibited high-glucose (HG)-induced mesenchymal activation and fibrosis via regulating miR-2113/rp11-982m15.8/Zeb1 pathway. 29654764 Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway 2018 heart endomyocardial_fibrosis mus_musculus Sra1 252891 Gene mRNA up-regulation NA NA dual-luciferase reporter assay etc. no Sra1 promoted cardiac myofibroblast activation by acting as a competitive endogenous rnas for miR-148b. 30694702 LncRNA SRA1 Promotes the Activation of Cardiac Myofibroblasts Through Negative Regulation of miR-148b 2019 heart cardiomegaly mus_musculus Agtrap 298646 Gene mRNA hyper-methylation NA NA PCR; Echocardiography yes The hypomethylation of AGTARP accompanying upregulation of ATRP expression in the myocardium is associated with the long-term inhibition of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) with prehypertensive losartan treatment. 28000857 Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats. 2017 heart cardiomegaly mus_musculus Atrap 11610 Gene mRNA hyper-methylation NA NA PCR; Echocardiography yes The hypomethylation of AGTARP accompanying upregulation of ATRP expression in the myocardium is associated with the long-term inhibition of left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) with prehypertensive losartan treatment. 28000857 Hypomethylation of Agtrap is associated with long-term inhibition of left ventricular hypertrophy in prehypertensive losartan-treated spontaneously hypertensive rats. 2017 heart endomyocardial_fibrosis homo_sapiens RASAL1 8437 Gene mRNA methylation NA NA CHIP; dual-luciferase reporter assay etc. no Transcriptional suppression of rasal1 through aberrant promoter methylation contributes to endothelial-to-mesenchymal transition (EndMT) and ultimately to progression of cardiac fibrosis. 25616414 Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiacfibrosis. 2015 heart cardiomegaly mus_musculus Myh7B 311570 Gene mRNA up-regulation NA CALCIUM SIGNALING PATHWAY Echocardiography no NA 32207065 MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway 2020 heart cardiomegaly homo_sapiens MYH7B 57644 Gene mRNA up-regulation NA CALCIUM SIGNALING PATHWAY Echocardiography no NA 32207065 MYH7B variants cause hypertrophic cardiomyopathy by activating the CaMK-signaling pathway 2020 kidney diabetic_nephropathy homo_sapiens PAQR9 344838 Gene mRNA up-regulation NRF2;HO-1 NF-KAPPA B SIGNALING PATHWAY qPCR; dual-luciferase reporter assay no "BLNC1 can affect inflammation, oxidative stress and renal fibrosis by NRF2/HO-1 and NF-KB pathways in diabetic nephropathies(dn)." 31632538 LncRNA Blnc1 expression and its effect on renal fibrosis in diabetic nephropathy 2019 kidney kidney_diseases mus_musculus Plekho1 67220 Gene mRNA down-regulation CX43 NRF2 SIGNALING PATHWAY immunofluorescence no "CKIP-1 acts downstream to CX43 on the activation of NRF2 signaling pathway to protect from renal fibrosis in diabetes, the mechanism of which might be related to the interaction of CKIP-1 with NRF2 through Cx43 carboxyl terminus (CT)." 33276097 CKIP-1 acts downstream to Cx43 on the activation of Nrf2 signaling pathway to protect from renal fibrosis in diabetes 2021 kidney diabetic_nephropathy mus_musculus Erbb4 13869 Gene mRNA up-regulation ERBB4-IR TGF-BETA SIGNALING PATHWAY NA no Erbb4-ir is a smad3-dependent lncrna that promotes renal fibrosis in type 2 diabetic nephropathy (T2DN) by suppressing miR-29b. 29222368 Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b 2018 kidney diabetic_nephropathy homo_sapiens ZEB1 6935 Gene mRNA down-regulation BMP7 TGF-BETA SIGNALING PATHWAY qPCR; dual-luciferase reporter assay no LncRNA ZEB1-AS1 inhibited high glucose-induced epithelial-mesenchymal transition (EMT) and fibrogenesis via regulating miR-216a-5p/bmp7 axis in diabetic nephropathy. 32294702 LncRNA ZEB1-AS1 inhibits high glucose-induced EMT and fibrogenesis by regulating the miR-216a-5p/BMP7 axis in diabetic nephropathy 2020 kidney diabetic_nephropathy mus_musculus Sirt3 64384 Gene mRNA down-regulation NA TGF-BETA SIGNALING PATHWAY NA no SIRT3 deficiency promotes abnormal glycolysis which is responsible for the fibrogenic pathway in diabetic kidney. 30250024 SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis 2018 kidney kidney_diseases mus_musculus Sox9 20682 Gene mRNA up-regulation NA TGF-BETA SIGNALING PATHWAY NA no Sox9 to intrinsic mechanisms of TGF-beta signaling in renal fibrosis and may have therapeutic potential for tissue fibrosis. 29158184 TGF-beta-mediated upregulation of Sox9 in fibroblast promotes renal fibrosis 2018 kidney kidney_failure_chronic mus_musculus Atp6Ap2 70495 Gene mRNA up-regulation NA WNT SIGNALING PATHWAY immunohistochemistry no The (pro)renin receptor (PRR) can promote kidney injury and fibrosis by amplifying wnt/beta-catenin signaling. 28270411 (Pro)renin Receptor Is an Amplifier of Wnt/ beta-Catenin Signaling in Kidney Injury and Fibrosis 2017 kidney kidney_diseases mus_musculus Cd226 225825 Gene mRNA down-regulation CD226 NA Masson's trichrome staining; RNA-seq analysis no The promotion of cd226 signaling on tregs is a therapeutic target for renal disease. 31802539 CD226 deficiency on regulatory T cells aggravates renal fibrosis via up-regulation of Th2 cytokines through miR-340 2020 liver liver_cirrhosis homo_sapiens HOTAIR 100124700 Gene mRNA dna methylation PTEN ERK; PI3K-AKT SIGNALING PATHWAY RT-PCR; dual-lucimmunofluorescenceerase reporter assay etc. no A histone deacetylase-4-dependent mechanism underlies the epigenetic silencing of mmp genes during tissue fibrogenesis. 28129115 HOTAIR Epigenetically Modulates PTEN Expression via MicroRNA-29b: A Novel Mechanism in Regulation of Liver Fibrosis 2017 liver hepatitis homo_sapiens IGF2 3481 Gene mRNA igf2 methylation IGF2 NA methylation analysis; dna extraction; bisulfite treatment of dna etc. no Angiogenic factor with g patch and fha domains 1 (aggf1) regulates liver fibrosis by modulating tgf-b signaling. 22902352 Insulin-like growth factor 2 gene methylation in peripheral blood mononuclear cells of patients with hepatitis C related cirrhosis or hepatocellular carcinoma 2012 liver liver_cirrhosis mus_musculus Fgf2 14173 Gene mRNA dna methylation NA P38 MAP KINASE RT-PCR; immunofluorescence etc. no "Ccn2 up-regulation in fibrotic or steatotic livers, or in culture-activated or ethanol-treated primary mouse hsc, is associated with a reciprocal down-regulation of microrna-214 (mir-214)." 25501710 Low-molecular-weight fibroblast growth factor 2 attenuates hepatic fibrosis by epigenetic down-regulation of Delta-like1 2015 liver liver_regeneration mus_musculus Pparg 25664 Gene mRNA dysregulation NA WNT SIGNALING PATHWAY RT-PCR; miRNA microarray chip detection etc. no "Concomitant epigenetic silencing of sox1 and sfrps through promoter hypermethylation is frequent in hccs, and this might contribute to abnormal activation of canonical wnt signal pathway." 22298767 Hepatic stellate cell-derived delta-like homolog 1 (DLK1) protein in liver regeneration 2012 liver liver_cirrhosis mus_musculus Ash1l 192195 Gene mRNA histone methylation ASH1 NA immunoblotting; qRT-PCR etc. no "Curcumin can up-regulate mir-29b expression, resulting in dnmt3b down-regulation in hscs and epigenetically-regulated pten involved in the suppression of activated hscs." 22488473 Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation 2012 liver liver_cirrhosis homo_sapiens ASH1L 55870 Gene mRNA histone methylation ASH1 NA qRT-PCR; xmiRNA microarray chip detection etc. no "Curcumin can up-regulate mir-29b expression, resulting in dnmt3b down-regulation in hscs and epigenetically-regulated pten involved in the suppression of activated hscs." 22488473 Histone methyltransferase ASH1 orchestrates fibrogenic gene transcription during myofibroblast transdifferentiation 2012 liver liver_cirrhosis mus_musculus Septin9 53860 Gene mRNA sept9 methylation 44448 NA qRT-PCR; immunohistochemistry etc. no Epigenetic repression of smad7 promotes the phosphorylation of smad2 and smad3 that may be an important molecular mechanism for perpetuated hsc activation and liver fibrosis. 27939986 Methylation of Septin9 mediated by DNMT3a enhances hepatic stellate cells activation and liver fibrogenesis 2017 liver liver_cirrhosis mus_musculus Sirt3 64384 Gene mRNA hyperacetylation of glycogen synthase kinase 3b (gsk3b) GSK3B TGF-BETA SIGNALING PATHWAY in vitro assay of sirt3 activity no "Ethanol caused dose and time-dependent increase in acetylation of histone h3 at lys9, but not at lys14 or lys18. Compared with hepatocytes the ac-h3-lys9 in hscs required longer ethanol exposure. Levels of me-h3-lys9 seemed to remain unaltered. Thus increase in ac-h3-lys9 represents a nuclear-chromatin modification event in hscs exposed to ethanol." 26667039 SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3B 2015 liver liver_cirrhosis homo_sapiens SIRT3 23410 Gene mRNA hyperacetylation of glycogen synthase kinase 3b (gsk3b) GSK3B TGF-BETA SIGNALING PATHWAY NA no "Ethanol caused dose and time-dependent increase in acetylation of histone h3 at lys9, but not at lys14 or lys18. Compared with hepatocytes the ac-h3-lys9 in hscs required longer ethanol exposure. Levels of me-h3-lys9 seemed to remain unaltered. Thus increase in ac-h3-lys9 represents a nuclear-chromatin modification event in hscs exposed to ethanol." 26667039 SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3B 2015 liver liver_cirrhosis mus_musculus Socs1 12703 Gene mRNA socs1 methylation SOCS1 TGF-BETA SIGNALING PATHWAY RT-PCR; immunohistostaining etc. no Genetic and pharmacologic disruptions of mecp2 or ezh2 reduced the fibrogenic characteristics of myofibroblasts and attenuated fibrogenesis. 15197228 SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis 2004 liver liver_cirrhosis homo_sapiens SOCS1 8651 Gene mRNA socs1 methylation SOCS1 TGF-BETA SIGNALING PATHWAY RT-PCR; immunohistostaining etc. no Genetic and pharmacologic disruptions of mecp2 or ezh2 reduced the fibrogenic characteristics of myofibroblasts and attenuated fibrogenesis. 15197228 SOCS1 is a suppressor of liver fibrosis and hepatitis-induced carcinogenesis 2004 liver liver_cirrhosis mus_musculus Cftr 12638 Gene mRNA histone deacetylase CFTR WNT SIGNALING PATHWAY miRNA microarray chip detection; immunoblotting; etc. no Hdac2 may play a pivotal role in hscs activation and liver fibrosis while deregulation of hdacs may serve as a novel mechanism underlying liver fibrosis. 17848139 The epigenetic signature of CFTR expression is co-ordinated via chromatin acetylation through a complex intronic element 2007 liver liver_cirrhosis homo_sapiens CFTR 1080 Gene mRNA histone deacetylase CFTR WNT SIGNALING PATHWAY miRNA microarray chip detection analysis; qmiRNA microarray chip detection; immunoblotting etc. no Hdac2 may play a pivotal role in hscs activation and liver fibrosis while deregulation of hdacs may serve as a novel mechanism underlying liver fibrosis. 17848139 The epigenetic signature of CFTR expression is co-ordinated via chromatin acetylation through a complex intronic element 2007 liver liver_cirrhosis mus_musculus CEBPA 1050 Gene mRNA sumoylation C; EBPA NA dual-lucimmunofluorescenceerase reporter assay; qRT-PCR; miRNA microarray chip detection etc. no Interaction between hdac3 and sumoylated c;Ebp alpha lxr alpha express negative regulation. 23639777 HDAC3 interacts with sumoylated C/EBPa to negatively regulate the LXRa expression in rat hepatocytes 2013 liver liver_cirrhosis mus_musculus Hgf 15234 Gene mRNA down-regulation NA NA enzyme-linked immunosorbent assay; immunohistochemistry etc. no Jmjd1a as a novel epigenetic regulator that modulates hsc activation and liver fibrosis through targeting ppary gene expression. 25380300 Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression 2014 liver liver_diseases_alcoholic mus_musculus Dnmt3b 13436 Gene mRNA dysregulation NA NA RT-PCR; immunohistochemical; dual-lucimmunofluorescenceerase reporter assay etc. no "Mecp2 silencing of h19 can alter the igf1r overexpression, thus contributing to hscs proliferation." 22841474 Epigenetic regulation of miR-34a expression in alcoholic liver injury 2012 liver liver_cirrhosis mus_musculus ctgf 100194970 Gene mRNA dysregulation CCN2 4'-UTR NA RT-PCR; immunohistochemical; dual-lucimmunofluorescenceerase reporter assay etc. no Mkl1 deficiency ameliorated bdl-induced liver fibrosis in mice as assessed by histological stainings and expression levels of pro-fibrogenic genes. 24122827 Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells 2014 liver liver_cirrhosis mus_musculus Dnmt1 13433 Gene mRNA dna methylation NA TGF-BETA SIGNALING PATHWAY immunofluorescence; qRT-PCR; etc. no Mrtf-a dependent histone h3k4 methylation to hsc activation. 24211420 Repression of Smad7 mediated by DNMT1 determines hepatic stellate cell activation and liver fibrosis in rats 2014 liver liver_cirrhosis mus_musculus Rasal1 19415 Gene mRNA rasal1 hypermethylation RASAL1 RAS SIGNALING PATHWAY MTT cell viability assay; RT-PCR etc. no Mrtf-a regulates liver fibrosis by epigenetically tuning the tgf-b signaling pathway in hscs. 22056649 MeCP2 controls the expression of RASAL1 in the hepatic fibrosis in rats 2011 liver liver_cirrhosis mus_musculus Nfkbia 18035 Gene mRNA dna methylation;mecp2 NA NA immunoblotting; qRT-PCR etc. no "Recombinant ctsh could break down hdac4 in the transfected cells and in vitro at acidic ph. In human cirrhotic liver, activated hscs express high levels of class iia hdacs but little ctsh." 16763620 Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis 2007 liver liver_cirrhosis mus_musculus H2az1 51788 Gene mRNA dna methylation H2A NA miRNA microarray chip detection; reconstitution of nucleosomes by salt dialysis; immunostaining etc. no "Reveals a new cross histone crosstalk, including h2a ubiquitin change control of h3k4 methylation and methylation, lead to the regulation of transcription initiation." 18172164 Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation 2008 liver liver_cirrhosis homo_sapiens H2AC20 8338 Gene mRNA dna methylation H2A NA in vivo electroporation; immunostaining; quantimmunofluorescenceication no "Reveals a new cross histone crosstalk, including h2a ubiquitin change control of h3k4 methylation and methylation, lead to the regulation of transcription initiation." 18172164 Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation 2008 liver non-alcoholic_fatty_liver_disease mus_musculus Ppp1cc 19047 Gene mRNA phosphatase pp1c PP1C PHOSPHO-EIF-2A KINASE-MEDIATED STRESS hyperinsulinemic-euglycemic clamp studies; immunoprecipitation; immunoblot etc. no Sirt2;Erk;C-myc axis in promoting hepatic fibrogenesis. Inhibition of the sirt2;Erk;C-myc axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis. 25888330 "Hepatocyte Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in Mice" 2015 liver non-alcoholic_fatty_liver_disease homo_sapiens PPP1CC 5501 Gene mRNA phosphatase pp1c PP1C PHOSPHO-EIF-2A KINASE-MEDIATED STRESS immunoprecipitation; immunoblot etc. no Sirt2;Erk;C-myc axis in promoting hepatic fibrogenesis. Inhibition of the sirt2;Erk;C-myc axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis. 25888330 "Hepatocyte Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in Mice" 2015 liver liver_cirrhosis mus_musculus Sirt2 64383 Gene mRNA histone deacetylase SIRT2 NA qRT-PCR; immunofluorescence; etc. no "Sumoylation of nrf2 and mafg enhances heterodimerization and increases gclc expression, which keeps hscs in a quiescent state. Antifibrotic agents require activation of gclc to fully exert their protective effect." 27125275 Inhibition of SIRT2 suppresses hepatic fibrosis 2016 liver liver_cirrhosis homo_sapiens SIRT2 22933 Gene mRNA histone deacetylase SIRT2 NA qRT-PCR; immunofluorescence; etc. no "Sumoylation of nrf2 and mafg enhances heterodimerization and increases gclc expression, which keeps hscs in a quiescent state. Antifibrotic agents require activation of gclc to fully exert their protective effect." 27125275 Inhibition of SIRT2 suppresses hepatic fibrosis 2016 liver liver_cirrhosis mus_musculus Creb1 12912 Gene mRNA creb-1 phosphorylation NA TGF-BETA SIGNALING PATHWAY qRT-PCR; immunofluorescence etc. no "The increase in opn induces hmgb1, which acts as a downstream alarmin driving collagen-i synthesis in hscs." 27840939 Post translational modification of creb-1 decreases collagen I expression by inhibiting the TGF B1 signaling pathway in rat hepatic stellate cells 2016 liver liver_cirrhosis homo_sapiens CREB1 1385 Gene mRNA creb-1 phosphorylation NA TGF-BETA SIGNALING PATHWAY RT-PCR; dual-lucimmunofluorescenceerase reporter assay etc. no "The increase in opn induces hmgb1, which acts as a downstream alarmin driving collagen-i synthesis in hscs." 27840939 Post translational modification of creb-1 decreases collagen I expression by inhibiting the TGF B1 signaling pathway in rat hepatic stellate cells 2016 liver liver_cirrhosis mus_musculus Pparg 25664 Gene mRNA histone methylation NA MECP2; EZH2; MIR132 miRNA microarray chip detection; q-PCR; RT-PCR etc. no "The reduction in h3k9me3 was accompanied by increased expression of long interspersed nucleotide elements 1 and short interspersed nucleotide elements b2, which is an indication of genomic instability." 19843474 MeCP2 controls an epigenetic pathway that promotes myofibroblast transdifferentiation and fibrosis 2010 lung Hypertension_Pulmonary homo_sapiens EDN1 1906 Gene mRNA down-regulation ET-1; TGFBR1 NA qRT-PCR; ELISA etc. no "35 MicroRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs was shown to be related to the disease pathogenesis by in silico analysis. Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease in CTEPH patients. ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by affecting ET-1 expression and the function of PAECs and PASMCs." 24978044 Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension 2014 lung Hypertension_Pulmonary homo_sapiens TGFBR1 7046 Gene mRNA down-regulation ET-1; TGFBR1 NA qRT-PCR; ELISA etc. no "35 MicroRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs was shown to be related to the disease pathogenesis by in silico analysis. Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease in CTEPH patients. ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by affecting ET-1 expression and the function of PAECs and PASMCs." 24978044 Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension 2014 lung Hypertension_Pulmonary homo_sapiens FGA 2243 Gene mRNA dysregulation NA NA Dual-luciferase reporter assay; etc. no "A deletion/insertion (Del/Ins) polymorphism of 28 base pairs (bp) in the 3' untranslated region (UTR) of fibrinogen alpha gene (FGA) was associated with thromboembolic diseases. The expression of FGA was regulated by miR-759 through its interaction at the polymorphic 3'UTR sequence, which was associated with the susceptibility to CTEPH. And the effect of miR-759 was stronger on the Ins allele than on the Del allele." 20677013 Susceptibility to chronic thromboembolic pulmonary hypertension may be conferred by miR-759 via its targeted interaction with polymorphic fibrinogen alpha gene 2010 lung pulmonary_hypertension mus_musculus Pdcd4 18569 Gene mRNA down-regulation NA NA qRT-PCR; Immunohistochemistry etc. no A microRNA-21-responsive PDCD4/caspase-3 pathway is existed in the pulmonary tissues that when active serves to promote endothelial apoptosis in vitro and PH in vivo. Direct PDCD4 knockout in mice (PDCD4(-/-) mice) potently blocked pulmonary caspase-3 activation and the development of chronic hypoxia. 24732886 Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/programmed cell death 4/caspase-3 axis 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens SERPINE1 5054 Gene mRNA up-regulation NA NA AEC purification; A549 cell wounding assay; Bleomycin exposure etc. no Accentuated impairment of plasminogen activation through PAI-1 overexpression leads to exuberant fibrosis after lung injury. 15308506 Plasminogen activator inhibitor-1 impairs alveolar epithelial repair by binding to vitronectin 2004 lung pulmonary_hypertension mus_musculus Igf1 16000 Gene mRNA dna methylation NA IGF-1/PAKT signaling pathway In vitro IGF-1 and inhibitor treatments; qRT-PCR; etc. no "After exposure to hypoxia, IGF-1 signaling is activated in pulmonary endothelial and smooth muscle cells in vitro, and the IGF-1 downstream signal pAKT(S473) is upregulated in lungs of neonatal mice. IGF-1 regulates ET-1 expression in pulmonary endothelial cells and that IGF-1 expression is regulated by histone deacetylases (HDACs). In addition, there is a differential cytosine methylation site in the IGF-1 promoter region in response to neonatal hypoxia. Moreover, inhibition of HDACs with apicidin decreases neonatal hypoxia-induced global DNA methylation levels in lungs and specific cytosine methylation levels around the pulmonary IGF-1 promoter region. Finally, HDAC inhibition with apicidin reduces chronic hypoxia-induced activation of IGF-1/pAKT signaling in lungs and attenuates right ventricular hypertrophy and pulmonary vascular remodeling. Taken together, we conclude that IGF-1, which is epigenetically regulated, is involved in the pathogenesis of pulmonary hypertension in neonatal mice." 25921925 IGF-1 signaling in neonatal hypoxia-induced pulmonary hypertension: Role of epigenetic regulation 2015 lung pulmonary_arterial_hypertension homo_sapiens BMP2 650 Gene mRNA up-regulation NA NA PKC activity; qRT-PCR; etc. no "An imbalance of bone morphogenetic protein-2/endothelin-1 systems may contribute to the progression of lung fibrosis, and to vascular remodeling in PAH." 21659661 Opposing effects of bone morphogenetic protein-2 and endothelin-1 on lung fibroblast chloride currents 2011 lung pulmonary_hypertension mus_musculus Bmpr2 12168 Gene mRNA up-regulation NA NA Animal experiments; Antagomir design etc. no AntagomiR-20a restores functional levels of BMPR2 in pulmonary arteries and prevents the development of vascular remodelling in an in vivo model for pulmonary hypertension. 22450430 AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens COL1A2 1278 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; etc. no "As expected, COL1A2, MMP1, and MMP7 were significantly higher and AGER was significantly lower in IPF and IPF-AEx compared with control samples, but there was no significant difference in their expression between IPF and IPF-AEx." 19363140 Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP1 4312 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; etc. no "As expected, COL1A2, MMP1, and MMP7 were significantly higher and AGER was significantly lower in IPF and IPF-AEx compared with control samples, but there was no significant difference in their expression between IPF and IPF-AEx." 19363140 Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens AGER 177 Gene mRNA down-regulation NA NA qRT-PCR; ELISA; etc. no "As expected, COL1A2, MMP1, and MMP7 were significantly higher and AGER was significantly lower in IPF and IPF-AEx compared with control samples, but there was no significant difference in their expression between IPF and IPF-AEx." 19363140 Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens DEFA4 1669 Gene mRNA up-regulation NA NA Pulmonary function testing; Quality characterization; Gene ontology and functional network analysis etc. no "Between the mild and severe IPF cohort , and between normal and severe disease, there is up-regulation of several other host defense genes including defensin A4 (DEFA4), cathelicidin antimicrobial peptide (CAMP), cathespin G (CTSG), and down-regulation of immunoglobulin heavy chain constant mu (IGHM)." 22761659 The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens CAMP 820 Gene mRNA up-regulation NA NA Pulmonary function testing; Quality characterization; Gene ontology and functional network analysis etc. no "Between the mild and severe IPF cohort , and between normal and severe disease, there is up-regulation of several other host defense genes including defensin A4 (DEFA4), cathelicidin antimicrobial peptide (CAMP), cathespin G (CTSG), and down-regulation of immunoglobulin heavy chain constant mu (IGHM)." 22761659 The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens CTSG 1511 Gene mRNA up-regulation NA NA Pulmonary function testing; Quality characterization; Gene ontology and functional network analysis etc. no "Between the mild and severe IPF cohort , and between normal and severe disease, there is up-regulation of several other host defense genes including defensin A4 (DEFA4), cathelicidin antimicrobial peptide (CAMP), cathespin G (CTSG), and down-regulation of immunoglobulin heavy chain constant mu (IGHM)." 22761659 The peripheral blood transcriptome identifies the presence and extent of disease in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis mus_musculus Bmper 73230 Gene mRNA dna methylation NA TGF-B/BMP signaling pathway Dual-luciferase reporter assay; ELISA etc. no "BMPER is highly expressed in human IPF lung fibroblasts compared to normal lung fibroblasts. Demethylation agent 5'-azacytidine decreased BMPER expression in fibroblasts, and attenuated the invasion and migration of IPF lung fibroblasts." 26442443 Methylation-mediated BMPER expression in fibroblast activation in vitro and lung fibrosis in mice in vivo 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Cav1 12389 Gene mRNA histone hypomethylation NA NA qRT-PCR; Immunoblot; MSP etc. no "Cav-1 gene silencing in lung fibroblasts is actively regulated by epigenetic mechanisms that involve histone modifications, in particular H3 lysine 4 trimethylation, whereas DNA methylation does not appear to be a primary mechanism." 27560128 Epigenetic Regulation of Caveolin-1 Gene Expression in Lung Fibroblasts 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL8 6355 Gene mRNA up-regulation NA CYTOKINE-CYTOKINE RECEPTOR INTERACTION signaling pathway qRT-PCR; ELISA; Immunofluorescence etc. no CCL8 is a candidate molecule for the differential diagnosis and prediction of survival. 28057004 Gene profile of fibroblasts identify relation of CCL8 with idiopathic pulmonary fibrosis 2017 lung idiopathic_pulmonary_fibrosis homo_sapiens SFTPA1 653509 Gene mRNA up-regulation NA NA "Change in FVC and DLco, and definition of deterioration; Changes in SP-A, SP-D, and KL-6; Statistical analysis etc." no Changes in serum SP-A reflected the outcomes of anti-fibrotic drug therapy. Serum SP-A has a potential as a biomarker of therapeutic outcomes of anti-fibrotic drugs. 32005219 Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis 2020 lung idiopathic_pulmonary_fibrosis homo_sapiens DNMT1 1786 Gene mRNA dysregulation NA NA qRT-PCR; Examination of DNA methylation patterns; Dual-luciferase reporter assay etc. no "Compared with control samples, miR-17~92 expression was reduced in lung biopsies and lung fibroblasts from patients with IPF, whereas DNMT-1 expression and methylation of the miR-17~92 promoter was increased. Several miRNAs from the miR-17~92 cluster targeted DNMT-1 expression resulting in a negative feedback loop. Similarly, miR-17~92 expression was reduced in the lungs of bleomycin-treated mice. Treatment with 5'-aza-2'-deoxycytidine in a murine bleomycin-induced pulmonary fibrosis model reduced fibrotic gene and DNMT-1 expression, enhanced miR-17~92 cluster expression, and attenuated pulmonary fibrosis." 23306545 Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis 2013 lung idiopathic_pulmonary_fibrosis mus_musculus Dnmt1 13433 Gene mRNA dysregulation NA NA qRT-PCR; Examination of DNA methylation patterns; Dual-luciferase reporter assay etc. no "Compared with control samples, miR-17~92 expression was reduced in lung biopsies and lung fibroblasts from patients with IPF, whereas DNMT-1 expression and methylation of the miR-17~92 promoter was increased. Several miRNAs from the miR-17~92 cluster targeted DNMT-1 expression resulting in a negative feedback loop. Similarly, miR-17~92 expression was reduced in the lungs of bleomycin-treated mice. Treatment with 5'-aza-2'-deoxycytidine in a murine bleomycin-induced pulmonary fibrosis model reduced fibrotic gene and DNMT-1 expression, enhanced miR-17~92 cluster expression, and attenuated pulmonary fibrosis." 23306545 Epigenetic regulation of miR-17~92 contributes to the pathogenesis of pulmonary fibrosis 2013 lung pulmonary_hypertension homo_sapiens CDKN1A 1026 Gene mRNA dna methylation NA NA BrdU incorporation assay; qRT-PCR; etc. no "Compared with controls, in high-altitude long-term hypoxia(LTH)fetus pulmonary arteries,global histone 4 acetylation and DNA methylation levels are reduced, accompanied by the loss of the cyclin-dependent kinase inhibitor p21. Treatment of LTH fetal PASMCs with histone deacetylase (HDAC) inhibitor trichostatin A decreased their proliferation rate, PDGF-induced cell migration, ERK1/2 activation and modulated global DNA methylation. Epigenetic alterations (reduced histone acetylation and DNA methylation) caused by chronic hypoxia leads to fetal PASMC proliferation and vessel remodeling associated with vascular proliferative disease and that this process is regulated by p21." 23043075 Pulmonary artery smooth muscle cell proliferation and migration in fetal lambs acclimatized to high-altitude long-term hypoxia: role of histone acetylation 2012 lung pulmonary_hypertension homo_sapiens CDKN1A 1026 Gene mRNA histone acetylation NA NA BrdU incorporation assay; qRT-PCR; etc. no "Compared with controls, in high-altitude long-term hypoxia(LTH)fetus pulmonary arteries,global histone 4 acetylation and DNA methylation levels are reduced, accompanied by the loss of the cyclin-dependent kinase inhibitor p21. Treatment of LTH fetal PASMCs with histone deacetylase (HDAC) inhibitor trichostatin A decreased their proliferation rate, PDGF-induced cell migration, ERK1/2 activation and modulated global DNA methylation. Epigenetic alterations (reduced histone acetylation and DNA methylation) caused by chronic hypoxia leads to fetal PASMC proliferation and vessel remodeling associated with vascular proliferative disease and that this process is regulated by p21." 23043075 Pulmonary artery smooth muscle cell proliferation and migration in fetal lambs acclimatized to high-altitude long-term hypoxia: role of histone acetylation 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens DHX58 79132 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens IDO1 3602 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens IFI44 10561 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CASP1 834 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PSMB9 5698 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PSMB10 5699 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens SLC15A3 51296 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens UBA7 7318 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens ASPA 443 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens SLC12A7 10723 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens TAP1 6890 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens IFI35 3430 Gene mRNA down-regulation NA NA Data compilation; Statistical analysis etc. no "Consistent with repression of processes involved in the immune/inflammatory response, the downregulated list was enriched with genes bearing binding sites for the Interferon Response Factor (IRF) transcription factor (11 genes out of 158 in the annotation: DHX58, IDO1, IFI44, CASP1, PSMB9, PSMB10, SLC15A3, UBA7, ASPA, SLC12A7, TAP1, p = 4.2E-6) And the Interferon Consensus Sequence Binding Protein (ICSBP) transcription factor (9 genes out of 203 in the annotation : IDO1, IFI44, PSMB9, SLC15A3, IFI35, UBA7, ASPA, SLC12A7, TAP1; P = 3.2E-3)." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CCN2 1490 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "CTGF, a member of the CCN protein family, is a highly potent extracellular matrix-associated mitogen. In vitro, CTGF induces collagen-1 expression in lung fibroblasts [20]. In vivo, overexpression of CTGF in fibroblasts drives fibrogenesis in multiple organs including the lung [21]. CTGF is overexpressed in IPF, with expression localized to alveolar epithelial cells and fibroblasts [22]. Consistent for a role of CTGF in IPF, a recent open-label uncontrolled study suggested that a monoclonal antibody targeting CTGF, FG-3019, may be beneficial in a subset of IPF patients in terms of lung function decline and imaging-assessed fibrotic changes [23]." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CTHRC1 115908 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Cthrc1 is expressed by fibroblasts, is involved in vascular remodeling, and decreases collagen matrix deposition . Cthrc1 is a downstream target of bone morphogenic protein-SMAD signaling, inhibits TGF-beta expression in neointimal lesion formation, and acts as a Wnt cofactor, possibly contributing to the promotion of cell motility. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Cthrc1 282836 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Cthrc1 is expressed by fibroblasts, is involved in vascular remodeling, and decreases collagen matrix deposition . Cthrc1 is a downstream target of bone morphogenic protein-SMAD signaling, inhibits TGF-beta expression in neointimal lesion formation, and acts as a Wnt cofactor, possibly contributing to the promotion of cell motility. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Pde1a 81529 Gene mRNA down-regulation Pde1a NA qRT-PCR; Dual-luciferase reporter assay; ELISA etc. no Cyclic nucleotide phosphodiesterase 1A (PDE1A) can stimulate lung fibroblasts to undergo myofibroblastic changes. MiR-541-5p expression is downregulated in TGF-B-treated lung fibroblasts and the rat pulmonary fibrosis model. Overexpression of miR-541-5p in lung fibroblasts inhibited mortality of human lung fibroblasts by targeting PDE1A. 28816543 MiR-541-5p regulates lung fibrosis by targeting cyclic nucleotide phosphodiesterase 1A 2017 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGS2 5743 Gene mRNA down-regulation NA NA qRT-PCR; Statistical analysis etc. no "Cyclooxygenase-2, a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E2, is downregulated in lung tissue from patients with idiopathic pulmonary fibrosis." 21319594 A haplotype of cyclooxygenase-2 gene is associated with idiopathic pulmonary fibrosis 2010 lung idiopathic_pulmonary_fibrosis homo_sapiens TCIM 56892 Gene mRNA dna hypermethylation NA NA qRT-PCR; Immunohistochemistry; etc. no "Decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE2 synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4." 26744410 Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis 2016 lung pulmonary_fibrosis mus_musculus Sftpc 20389 Gene mRNA histone acetylation NA NA qRT-PCR; Immunohistochemistry etc. no Decreased expression of SFTPC by TGF-B1 treatment was restored by TSA via hyperacetylation of histone H4 in the promoter region. TSA partially attenuated pulmonary fibrosis and increased Sftpc mRNA in ATII. 26151196 Histone deacetylase inhibitor restores surfactant protein-C expression in alveolar-epithelial type II cells and attenuates bleomycin-induced pulmonary fibrosis in vivo 2015 lung cystic_fibrosis homo_sapiens HMOX1 3162 Gene mRNA dna methylation NA NA DNA methylation correlations in CF cells; DNA methylation analysis in NEC; DNA methylation at HMOX1 was not associated with nearby polymorphisms etc. no DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; Other changes may result in small expression variations that collectively modulate the lung disease severity. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. 28289476 DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis 2017 lung cystic_fibrosis homo_sapiens EDNRA 1909 Gene mRNA dna methylation NA NA DNA methylation correlations in CF cells; DNA methylation analysis in NEC; DNA methylation at HMOX1 was not associated with nearby polymorphisms etc. no DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; Other changes may result in small expression variations that collectively modulate the lung disease severity. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. 28289476 DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis 2017 lung cystic_fibrosis homo_sapiens GSTM3 2947 Gene mRNA dna methylation NA NA DNA methylation correlations in CF cells; DNA methylation analysis in NEC; DNA methylation at HMOX1 was not associated with nearby polymorphisms etc. no DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; Other changes may result in small expression variations that collectively modulate the lung disease severity. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. 28289476 DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis 2017 lung pulmonary_fibrosis mus_musculus Il6 16193 Gene mRNA down-regulation Il-6 NA qRT-PCR; ELISA etc. no Down-regulation of miR-149 and up-regulation of IL-6 might be involved in the progression of silica-induced pulmonary fibrosis; MiR-149 could negatively regulate IL-6 expression. 24641842 Regulatory effect of miR-149 on interleukin-6 expression in silica-induced pulmonary fibrosis 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens ABAT 18 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens FAM168B 130074 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PPRC1 23082 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens DVL3 1857 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens ZMIZ1 57178 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens SLC38A1 81539 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens XYLT1 64131 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens ARL4A 10124 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens ADO 84890 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens FAM168A 23201 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PLEKHA3 65977 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens AUTS2 26053 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "Enrichment in genes putatively regulated by the microRNA miR-153 was observed among upregulated transcripts (13 genes out of 153 in the annotation: ABAT, FAM168B, PPRC1, DVL3, ZMIZ1, MFAPL3, SLC38A1, XYLT1, ARL4A, ADO, FAM168A, PLEKHA3, AUTS2, p = 1.2E-2). Functional annotation analysis did not identify enrichment of Gene Ontology, pathway, functional class nor transcription factor binding site categories among transcripts upregulated in IPF fibroblasts." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung pulmonary_arterial_hypertension homo_sapiens CCL24 6369 Gene mRNA up-regulation NA NA Biochemical staining; Immunostaining; ELISA etc. no Eotaxin-2/CCL24 but not eotaxin-3/CCL26 stimulated human lung fibroblast proliferation and collagen synthesis. 20143648 Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts 2010 lung pulmonary_arterial_hypertension homo_sapiens CCL26 10344 Gene mRNA up-regulation NA NA Biochemical staining; Immunostaining; ELISA etc. no Eotaxin-3/CCL26 but not eotaxin-2/CCL24 promoted fibroblast migration. 20143648 Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts 2010 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL10 3627 Gene mRNA histone modification NA NA qRT-PCR; ELISA; etc. no Epigenetic dysregulation involving interactions between histone deacetylation and hypermethylation is responsible for targeted repression of IP-10 and potentially other antifibrotic genes in fibrotic lung disease and that this is amenable to therapeutic targeting. 20404089 Repression of IP-10 by interactions between histone deacetylation and hypermethylation in idiopathic pulmonary fibrosis 2010 lung idiopathic_pulmonary_fibrosis mus_musculus Smad3 17127 Gene mRNA histone hyperacetylation NA NA Immunofluorescence; qRT-PCR etc. no ERK5 regulates TGF-B1-induced fibrogenic signaling via Smad3 acetylation. 24095924 ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation 2013 lung idiopathic_pulmonary_fibrosis mus_musculus Mapk7 23939 Gene mRNA histone hyperacetylation NA NA Immunofluorescence; qRT-PCR etc. no ERK5 regulates TGF-B1-induced fibrogenic signaling via Smad3 acetylation. 24095924 ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation 2013 lung pulmonary_hypertension homo_sapiens SOD3 6649 Gene mRNA histone acetylation NA JAK2/STAT3 signaling pathway; P44/42 ERK 1/2 signaling pathway ROS Measurement; Mtt assay; EC-SOD Immunoprecipitation etc. no "Exposure of HPAECs to scriptaid, N[4 [(hydroxyamino)carbonyl] phenyl]-a-(1-methylethyl)-benzeneacetamide, and trichostatin A for 24 hours induced expression of extracellular superoxide dismutase (EC-SOD), whereas expression of the prooxidant gene NADPH oxidase 4 was decreased. Induction of EC-SOD expression was attenuated by the Janus kinase 2 protein kinase inhibitor AG490 and by silencing Janus kinase 2 expression. Augmentation of EC-SOD expression using scriptaid was associated with increased histone H3 (Lys27) acetylation and H3 (Lys4) trimethylation at the gene promoter." 25749103 Regulation of Oxidative Stress in Pulmonary Artery Endothelium Modulation of Extracellular Superoxide Dismutase and NOX4 Expression Using Histone Deacetylase Class I Inhibitors 2015 lung pulmonary_hypertension homo_sapiens NOX4 50507 Gene mRNA histone acetylation NA JAK2/STAT3 signaling pathway; P44/42 ERK 1/2 signaling pathway ROS Measurement; Mtt assay; EC-SOD Immunoprecipitation etc. no "Exposure of HPAECs to scriptaid, N[4 [(hydroxyamino)carbonyl] phenyl]-a-(1-methylethyl)-benzeneacetamide, and trichostatin A for 24 hours induced expression of extracellular superoxide dismutase (EC-SOD), whereas expression of the prooxidant gene NADPH oxidase 4 was decreased. Induction of EC-SOD expression was attenuated by the Janus kinase 2 protein kinase inhibitor AG490 and by silencing Janus kinase 2 expression. Augmentation of EC-SOD expression using scriptaid was associated with increased histone H3 (Lys27) acetylation and H3 (Lys4) trimethylation at the gene promoter." 25749103 Regulation of Oxidative Stress in Pulmonary Artery Endothelium Modulation of Extracellular Superoxide Dismutase and NOX4 Expression Using Histone Deacetylase Class I Inhibitors 2015 lung Pulmonary_Disease_Chronic_Obstructive rattus_norvegicus Cdkn2a 25163 Gene mRNA promoter hypermethylation NA NA qRT-PCR; Immunohistochemistry etc. no "Exposure to hyperoxia may induce p16 promoter hypermethylation in lung tissues in premature rats, and methylation risk increases as exposure extends. P16 promoter methylation induced by hyperoxia may be one of the mechanisms for low p16 mRNA and protein expression." 20113419 Detection of p16 promoter methylation in premature rats with chronic lung disease induced by hyperoxia 2010 lung idiopathic_pulmonary_fibrosis homo_sapiens SMAD4 4089 Gene mRNA promoter hypermethylation NA NA qRT-PCR; PCR-SSCP etc. no Expression levels of Smad4 were significantly lower in tumors from lung cancer/IPF patients than in those from lung cancer patients without IPF or in lung cancer cell lines. The loss of the growth inhibitory response to TGF-B signaling may be crucial in pulmonary carcinogensis or in the progression of lung cancer in IPF patients in whom TGF-B is overexpressed; Hypermethylation of the Smad4 promoter region may be one mechanism by which this occurs. 21475793 Reduced transcription of the Smad4 gene during pulmonary carcinogenesis in idiopathicpulmonary fibrosis 2009 lung pulmonary_fibrosis mus_musculus Tsc1 64930 Gene mRNA down-regulation NA NA Immunohistochemistry; Immunofluorescence; etc. no "Expression of TSC1 and TSC2 in fibrotic mice lung was reduced and in HELF cells with TGF-B1stimulation. In addition, overexpression of TSC1 or TSC2 decreased cell proliferation and differentiation. Reduced expression of TSC1 and TSC2 caused by TGF-B1 is associated with the promoter methylation status of TSC1 and TSC2. Expression of TSC1 and TSC2 can be repressed by MeCP2, which regulates HELF cell differentiation and proliferation as myofibroblasts and lead to PF." 28041914 Repression of TSC1/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation 2016 lung pulmonary_fibrosis mus_musculus Tsc2 22084 Gene mRNA down-regulation NA NA Immunohistochemistry; Immunofluorescence; etc. no "Expression of TSC1 and TSC2 in fibrotic mice lung was reduced and in HELF cells with TGF-B1stimulation. In addition, overexpression of TSC1 or TSC2 decreased cell proliferation and differentiation. Reduced expression of TSC1 and TSC2 caused by TGF-B1 is associated with the promoter methylation status of TSC1 and TSC2. Expression of TSC1 and TSC2 can be repressed by MeCP2, which regulates HELF cell differentiation and proliferation as myofibroblasts and lead to PF." 28041914 Repression of TSC1/TSC2 mediated by MeCP2 regulates human embryo lung fibroblast cell differentiation and proliferation 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Ezh2 14056 Gene mRNA up-regulation NA NA qRT-PCR; Immunohistochemistry etc. no EZH2 was upregulated in the lungs of patients with IPF and in mice with bleomycin-induced lung fibrosis. EZH2 induces the differentiation of fibroblasts to myofibroblasts by enhancing Smad2/3 nuclear translocation. 27582065 EZH2 enhances the differentiation of fibroblasts into myofibroblasts in idiopathic pulmonary fibrosis 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Col1a1 12842 Gene mRNA dysregulation Col1a1 NA qRT-PCR; Dual-luciferase reporter assay etc. no "H19 play a promotive role in bleomycin-induced epithelial-mesenchymal transition of alveolar epithelial cell through miR-29b regulation. H19 expression was positively correlated with COL1A1 and Acta2 expression; H19 knockdown inhibited COL1A1 and Acta2 expression. Moreover, H19 interacted with miR-29b through directly binding to the 3'UTR; MiR-29b inhibited COL1A1 expression by directly binding to the 3'UTR. In conclusion, we revealed the promotive effect of H19 on BLM-induced IPF, and demonstrated the mechanism by which H19/miR-29b interaction exerts its effect on regulating pulmonary fibrosis." 27613097 The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGS2 5743 Gene mRNA histone acetylation NA NA HDAC activity assay; ChIp assay; Reporter gene assay etc. no "HDAC inhibitors and the overexpression of HATs restored cytokine-induced COX-2 mRNA and protein expression in F-IPF. The results demonstrate that epigenetic abnormality in the form of histone hypoacetylation is responsible for diminished COX-2 expression in IPF. Diminished cyclooxygenase 2 (COX-2) expression in fibroblasts, with a resultant defect in the production of the antifibrotic mediator prostaglandin E(2), promote pathogenesis of idiopathic pulmonary fibrosis (IPF)." 19487460 Defective histone acetylation is responsible for the diminished expression of cyclooxygenase 2 in idiopathic pulmonary fibrosis 2009 lung pulmonary_hypertension rattus_norvegicus Nox1 114243 Gene mRNA histone deacetylation NA NA Engineered CRISPR-Cas9 and DNA constructs; qRT-PCR; Promoter activity assays etc. no "HDAC inhibitors block the binding of RNA polymerase II and the histone acetyltransferase p300 to the Nox2, Nox4 and Nox5 promoter regions and decrease histones activation marks (H3K4me3 and H3K9ac) at these promoter sites. In a monocrotaline (MCT) rat model of PAH, multiple HDAC isoforms are upregulated in isolated pulmonary arteries, and HDAC inhibitors attenuate Nox expression in isolated pulmonary arteries and reduce indices of PAH. In conclusion, HDAC inhibitors potently suppress Nox gene expression both in vitro and in vivo via epigenetically regulating chromatin accessibility." 27498117 Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension 2016 lung pulmonary_hypertension rattus_norvegicus Cybb 66021 Gene mRNA histone deacetylation NA NA Engineered CRISPR-Cas9 and DNA constructs; qRT-PCR; Promoter activity assays etc. no "HDAC inhibitors block the binding of RNA polymerase II and the histone acetyltransferase p300 to the Nox2, Nox4 and Nox5 promoter regions and decrease histones activation marks (H3K4me3 and H3K9ac) at these promoter sites. In a monocrotaline (MCT) rat model of PAH, multiple HDAC isoforms are upregulated in isolated pulmonary arteries, and HDAC inhibitors attenuate Nox expression in isolated pulmonary arteries and reduce indices of PAH. In conclusion, HDAC inhibitors potently suppress Nox gene expression both in vitro and in vivo via epigenetically regulating chromatin accessibility." 27498117 Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension 2016 lung pulmonary_hypertension rattus_norvegicus Nox4 95431 Gene mRNA histone deacetylation NA NA Engineered CRISPR-Cas9 and DNA constructs; qRT-PCR; Promoter activity assays etc. no "HDAC inhibitors block the binding of RNA polymerase II and the histone acetyltransferase p300 to the Nox2, Nox4 and Nox5 promoter regions and decrease histones activation marks (H3K4me3 and H3K9ac) at these promoter sites. In a monocrotaline (MCT) rat model of PAH, multiple HDAC isoforms are upregulated in isolated pulmonary arteries, and HDAC inhibitors attenuate Nox expression in isolated pulmonary arteries and reduce indices of PAH. In conclusion, HDAC inhibitors potently suppress Nox gene expression both in vitro and in vivo via epigenetically regulating chromatin accessibility." 27498117 Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension 2016 lung pulmonary_arterial_hypertension rattus_norvegicus Hdac5 84580 Gene mRNA histone deacetylation NA NA Immunohistochemistry; qRT-PCR etc. no "HDAC1 and HDAC5 protein levels were elevated in lungs from human idiopathic pulmonary arterial hypertension and in lungs and right ventricles from rats exposed to hypoxia. Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat. Exposure to valproic acid and suberoylanilide hydroxamic acid was associated with increased levels of p21 and FOXO3 and reduced expression of survivin. The significantly higher levels of expression of cKIT, monocyte chemoattractant protein-1, interleukin-6, stromal-derived factor-1, platelet-derived growth factor-b, and S100A4 in R-cells were downregulated by valproic acid and suberoylanilide hydroxamic acid treatment." 22711276 Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid 2012 lung pulmonary_arterial_hypertension rattus_norvegicus Hdac1 297893 Gene mRNA histone deacetylation NA NA Immunohistochemistry; qRT-PCR etc. no "HDAC1 and HDAC5 protein levels were elevated in lungs from human idiopathic pulmonary arterial hypertension and in lungs and right ventricles from rats exposed to hypoxia. Both valproic acid, a class I HDAC inhibitor, and suberoylanilide hydroxamic acid (vorinostat), an inhibitor of class I, II, and IV HDACs, mitigated the development of and reduced established hypoxia-induced pulmonary hypertension in the rat. Exposure to valproic acid and suberoylanilide hydroxamic acid was associated with increased levels of p21 and FOXO3 and reduced expression of survivin. The significantly higher levels of expression of cKIT, monocyte chemoattractant protein-1, interleukin-6, stromal-derived factor-1, platelet-derived growth factor-b, and S100A4 in R-cells were downregulated by valproic acid and suberoylanilide hydroxamic acid treatment." 22711276 Histone deacetylation inhibition in pulmonary hypertension: therapeutic potential of valproic acid and suberoylanilide hydroxamic acid 2012 lung Familial_Primary_Pulmonary_Hypertension homo_sapiens SMAD9 4093 Gene mRNA dysregulation NA NA etc. no "Heritable pulmonary arterial hypertension (HPAH) associated BMPR2 and SMAD9 mutation completely abrogated noncanonical Smad-mediated microRNA (miR) processing, leading to miR-21 downregulation, contributing to vascular cell proliferation." 21920918 Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8 2011 lung Familial_Primary_Pulmonary_Hypertension homo_sapiens BMPR2 659 Gene mRNA dysregulation NA NA etc. no "Heritable pulmonary arterial hypertension (HPAH) associated BMPR2 and SMAD9 mutation completely abrogated noncanonical Smad-mediated microRNA (miR) processing, leading to miR-21 downregulation, contributing to vascular cell proliferation." 21920918 Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8 2011 lung Idiopathic_Pulmonary_Arterial_Hypertension homo_sapiens SOD3 6649 Gene mRNA histone deacetylation NA NA qRT-PCR; SOD Activity etc. no "Histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression." 27233998 Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Asic2 11418 Gene mRNA down-regulation Tgf-beta1; Ets1 NA In Silico Identification of miRNA Binding Sites; Measurement of Cytokines and Collagen Content etc. no "Hsa-miR-326 regulates TGF-B1 expression and that hsa-miR-326 levels are inversely correlated to TGF-B1 protein levels in multiple human cell lines.MiR-326 was found to down-regulate profibrotic genes, such as Ets1, Smad3, and matrix metalloproteinase 9, whereas it up-regulates antifibrotic genes, such as Smad7." 24279830 MicroRNA-326 Regulates Profibrotic Functions of Transforming Growth Factor-B in Pulmonary Fibrosis 2014 lung pulmonary_hypertension mus_musculus Pdlim5 56376 Gene mRNA down-regulation Pdlim5? NA Isolation of Mouse PASMC; Lentivirus-based miR-17?92 Overexpression in HPASMC; PDLIM5 3'-Untranslated Region Luciferase Reporter Assay no "Human PASMC (HPASMC) from patients with PAH expressed decreased levels of the miR-17 92 cluster, TGF-B, and SMC markers. Knockdown of Smad3 but not Smad2 prevented miR-17 92-induced expression of SMC markers. SMC-specific knockout of miR-17 92 attenuated hypoxia-induced pulmonary hypertension (PH) in mice, whereas reconstitution of miR-17 92 restored hypoxia-induced PH in these mice. PDLIM5 is a direct target of miR-17/20a, and hypertensive HPASMC and mouse PASMC expressed elevated PDLIM5 levels. Suppression of PDLIM5 increased expression of SMC markers and enhanced TGF-B/Smad2/3 activity in vitro and enhanced hypoxia-induced PH in vivo, whereas overexpression of PDLIM5 attenuated hypoxia-induced PH." 25647182 Loss of MicroRNA-17 92 in Smooth Muscle Cells Attenuates Experimental Pulmonary Hypertension via Induction of PDZ and LIM Domain 5 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR9 54106 Gene mRNA dna hypomethylation NA NA qRT-PCR; etc. no "Hypomethylated CpG DNA drives the rapid progression of fibrotic lung disease through the differentiation of pulmonary fibroblasts into myofibroblasts through a TLR9-dependent mechanism; Toll-like receptor 9 (TLR9)-dependent macroautophagy drive the loss of Argonaute (AGO)1 and AGO2, leading to aberrant micro RNA processing, thereby promoting the rapid progression of IPF." 22802293 Epigenetic mechanisms through which Toll-like receptor-9 drives idiopathic pulmonary fibrosis progression 2012 lung pulmonary_hypertension mus_musculus Bmpr2 12168 Gene mRNA up-regulation NA NA Network-based analyses; Right heart catheterization and physiological measurements etc. no "Hypoxia and BMP receptor type 2 signaling independently upregulate miR-21 in cultured pulmonary arterial endothelial cells. In a reciprocal feedback loop, miR-21 downregulates BMP receptor type 2 expression. Furthermore, miR-21 directly represses RhoB expression and Rho-kinase activity, inducing molecular changes consistent with decreased angiogenesis and vasodilation. In vivo, miR-21 is upregulated in pulmonary tissue from several rodent models of PH and in humans with PH. On induction of disease in miR-21-null mice, RhoB expression and Rho-kinase activity are increased, accompanied by exaggerated manifestations of PH." 22371328 MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach 2012 lung pulmonary_arterial_hypertension rattus_norvegicus Tp73 362675 Gene mRNA dysregulation NA NA Immunohistochemistry; qRT-PCR; Immunofluorescence etc. no "Hypoxia increases type I collagen prolyl-4-hydroxylase [C-P4H(I)], which leads to prolyl-hydroxylation and accumulation of Argonaute2 (Ago2). Hydroxylation of Ago2 is required for the association of Ago2 with heat shock protein 90 (Hsp90), which is necessary for the loading of microRNAs (miRNAs) into the RISC, and translocation to stress granules (SGs). We demonstrate that hydroxylation of Ago2 increases the level of miRNAs and increases the endonuclease activity of Ago2. In summary, this study identifies hypoxia as a mediator of the miRNA-dependent gene silencing pathway through posttranslational modification of Ago2, which might be responsible for pulmonary artery hypertension (PAH)." 21969601 Hypoxia potentiates microRNA-mediated gene silencing through posttranslational modification of Argonaute2 2011 lung pulmonary_hypertension homo_sapiens DDAH1 23576 Gene mRNA up-regulation DDAH1 NA qRT-PCR; Dual-luciferase reporter assay etc. no "Hypoxia inhibited DDAH1 and DDAH2 expression and increased ADMA levels in cultured human pulmonary endothelial cells. In contrast, in human pulmonary smooth muscle cells, only DDAH2 was reduced whereas ADMA levels remained unchanged. Endothelium-specific down-regulation of DDAH1 by miR-21 in hypoxia induced endothelial dysfunction and was prevented by overexpression of DDAH1 and miR-21 blockade. DDAH1, but not DDAH2, mRNA levels were reduced, whereas miR-21 levels were elevated in lung tissues from patients with pulmonary arterial hypertension and mice with pulmonary hypertension exposed to 2 weeks of hypoxia." 24895913 MiR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia 2014 lung pulmonary_hypertension mus_musculus Ddah1 69219 Gene mRNA up-regulation Ddah1 NA qRT-PCR; Dual-luciferase reporter assay etc. no "Hypoxia inhibited DDAH1 and DDAH2 expression and increased ADMA levels in cultured human pulmonary endothelial cells. In contrast, in human pulmonary smooth muscle cells, only DDAH2 was reduced whereas ADMA levels remained unchanged. Endothelium-specific down-regulation of DDAH1 by miR-21 in hypoxia induced endothelial dysfunction and was prevented by overexpression of DDAH1 and miR-21 blockade. DDAH1, but not DDAH2, mRNA levels were reduced, whereas miR-21 levels were elevated in lung tissues from patients with pulmonary arterial hypertension and mice with pulmonary hypertension exposed to 2 weeks of hypoxia." 24895913 MiR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens MNT 4335 Gene mRNA down-regulation MNT NA qRT-PCR; Immunohistochemistry etc. no "Hypoxia potently stimulates miR-210 expression via HIF-2a, and high miR-210 expression drives fibroblast proliferation by repressing the c-myc inhibitor, MNT." 24951777 MiR-210 promotes IPF fibroblast proliferation in response to hypoxia 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens EPAS1 2034 Gene mRNA down-regulation MNT NA qRT-PCR; Immunohistochemistry etc. no "Hypoxia potently stimulates miR-210 expression via HIF-2a, and high miR-210 expression drives fibroblast proliferation by repressing the c-myc inhibitor, MNT." 24951777 MiR-210 promotes IPF fibroblast proliferation in response to hypoxia 2014 lung pulmonary_hypertension rattus_norvegicus Kcnq5 259273 Gene mRNA up-regulation Kcnq5 NA qRT-PCR; Dual-luciferase reporter assay; etc. no "Hypoxia produced a significant increase of the miR-190 level in the pulmonary artery (PA). MiR-190 mimic enhanced enhanced the pulmonary vasoconstriction responses to phenylephrine (PE) and KCl. The voltage-gated K(+) channel subfamily member, Kcnq5 was a target for miR-190. MiR-190 appears to be a positive regulator of Ca(2+) influx, and plays an important role in hypoxic pulmonary vascular constriction." 24446351 MicroRNA-190 regulates hypoxic pulmonary vasoconstriction by targeting a voltage-gated K channel in arterial smooth muscle cells 2014 lung pulmonary_hypertension rattus_norvegicus Cacna1c 24239 Gene mRNA down-regulation L-TYPE CALCIUM CHANNEL-A1C; INSULIN GROWTH FACTOR 1 RECEPTOR NA Dual-luciferase reporter assay; Mtt assay; etc. no "Hypoxia produced a significant inhibition of miRNA-328 expression, which was involved in PA vasoconstriction and remodeling. Overexpressing miRNA-328 in the transgenic mice remarkably decreased the right ventricular systolic pressure and PA wall thickness under both normoxia and hypoxia. MiRNA-328 inhibited L-type calcium channel-a1C expression through a miRNA-328 binding site within the 3' untranslational region of L-type calcium channel-a1C. The L-type calcium channel-a1C inhibition attenuated the PA response to KCl. Furthermore, miRNA-328 suppressed the insulin growth factor 1 receptor, ultimately leading to apoptosis of pulmonary arterial smooth muscle cells." 22392900 The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-a1C 2012 lung pulmonary_hypertension rattus_norvegicus Igf1r 25718 Gene mRNA down-regulation L-TYPE CALCIUM CHANNEL-A1C; INSULIN GROWTH FACTOR 1 RECEPTOR NA Dual-luciferase reporter assay; Mtt assay; etc. no "Hypoxia produced a significant inhibition of miRNA-328 expression, which was involved in PA vasoconstriction and remodeling. Overexpressing miRNA-328 in the transgenic mice remarkably decreased the right ventricular systolic pressure and PA wall thickness under both normoxia and hypoxia. MiRNA-328 inhibited L-type calcium channel-a1C expression through a miRNA-328 binding site within the 3' untranslational region of L-type calcium channel-a1C. The L-type calcium channel-a1C inhibition attenuated the PA response to KCl. Furthermore, miRNA-328 suppressed the insulin growth factor 1 receptor, ultimately leading to apoptosis of pulmonary arterial smooth muscle cells." 22392900 The microRNA-328 regulates hypoxic pulmonary hypertension by targeting at insulin growth factor 1 receptor and L-type calcium channel-a1C 2012 lung pulmonary_fibrosis homo_sapiens TGFB1 7040 Gene mRNA histone hyperacetylation NA NF-kappaB signaling pathway; AP-1 signaling pathway qRT-PCR; ELISA etc. no "IL-1beta-stimulated transcription of TGF-Beta1 is temporally regulated by NF-kappaB and AP-1 and involves histone H3, H4 hyperacetylation at distinct promoter sites." 16365456 NF-kappaB and activator protein 1 response elements and the role of histone modifications in IL-1beta-induced TGF-Beta1 gene transcription 2006 lung cystic_fibrosis homo_sapiens CXCL8 3576 Gene mRNA up-regulation NA NA LD; Dual-luciferase reporter assay etc. no IL8 variants modify CF lung disease severity and have functional consequences. 18563170 Modulation of cystic fibrosis lung disease by variants in interleukin-9 2008 lung pulmonary_fibrosis homo_sapiens CDH1 999 Gene mRNA promoter hypermethylation NA NA Immunofluorescence; qRT-PCR etc. no "In bronchial epithelial cells, NiCl(2) induced EMT phenotype marker alterations such as up-regulation of fibronectin and down-regulation of E-cadherin. In addition, the potent antioxidant N-acetylcysteine blocked EMT and expression of HIF-1a induced by NiCl(2), whereas the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine restored the down-regulation of E-cadherin induced by NiCl(2). Promoter hypermethylation of E-cadherin was also induced by NiCl(2). Specifically, NiCl(2) induces down-regulation of E-cadherin by reactive oxygen species generation and promoter hypermethylation." 22648416 Nickel-induced epithelial-mesenchymal transition by reactive oxygen species generation and E-cadherin promoter hypermethylation 2012 lung cystic_fibrosis mus_musculus Cav1 12389 Gene mRNA down-regulation Cav1 AKT/MIR-199A-5P/CAV1 signaling pathway In vivo experiment and BAL fluid collection and analysis; qRT-PCR; etc. no "In CF macrophage, activated PI3K/AKT pathway increase miR-199a-3p expression, reduce expression of CAV1, leading to increased TLR4 signaling and inflammation. Celecoxib re-establishes the AKT/miR-199a-5p/CAV1 axis in CF macrophages, and ameliorates lung hyper-inflammation in Cftr-deficient mice." 25665524 Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Ptgs2 19225 Gene mRNA histone hyperacetylation NA NA qRT-PCR; Immunofluorescence etc. no "In DADS-treatedlung fibroblasts, upregulated expression of COX-2 was a result of increased level of histone 3 acetylation at COX-2 locus, which lead to inhibition of proliferation and transdifferentiation of lung fibroblasts." 24756243 Diallyl disulfide inhibits proliferation and transdifferentiation of lung fibroblasts through induction of cyclooxygenase and synthesis of prostaglandin E 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Col3a1 12825 Gene mRNA histone hyperacetylation NA NA qRT-PCR; Immunofluorescence; Immunohistochemistry etc. no "In fibrotic lung fibroblasts, reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression." 24084714 Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts 2013 lung idiopathic_pulmonary_fibrosis homo_sapiens COL3A1 1281 Gene mRNA histone hyperacetylation NA NA qRT-PCR; Immunofluorescence; Immunohistochemistry etc. no "In fibrotic lung fibroblasts, reduced expression of COL3A1 by SAHA is with increased association of the repressive chromatin marker, H3K27Me3, and decreased association of the active chromatin marker, H3K9Ac. HDACi SAHA alters the chromatin associated with COL3A1, resulting in its decreased expression." 24084714 Histone Deacetylase Inhibition Downregulates Collagen 3A1 in Fibrotic Lung Fibroblasts 2013 lung pulmonary_hypertension mus_musculus Pparg 25664 Gene mRNA up-regulation NA NA Dual-luciferase reporter assay; qRT-PCR; etc. no "In hypoxia-induced PAH,miR-27a and ET-1 are increased, whereas PPARY is reduced. PPARY ligand rosiglitazone (RSG, 10 mg/kg/d) treatment could inhibit miR-27a expression.Overexpression of miR-27a or PPARY knockdown increased HPAEC proliferation and ET-1 expression and decreased PPARY levels. MiR-27a levels were upregulated in lungs from endothelial-targeted PPARY knockout (ePPARY KO) mice. Knockdown of either SP1 or EGR1 was sufficient to significantly attenuate miR-27a expression in HPAECs. Collectively, these studies provide novel evidence that miR-27a and PPARY mediate mutually repressive actions in hypoxic pulmonary vasculature and that targeting PPARY may represent a novel therapeutic approach in PH to attenuate proliferative mediators that stimulate proliferation of pulmonary vascular cells." 24244514 Hypoxia mediates mutual repression between microRNA-27a and PPARY in the pulmonary vasculature 2013 lung idiopathic_pulmonary_fibrosis homo_sapiens WNT1 7471 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "In IPF lung specimens, Wnt1, 7b, and 10b mRNA levels were markedly upregulated (log-fold change of 1.19+-0.43, 1.05+-0.43, And 1.58+-0.59, Respectively), whereas Wnt3a was significantly downregulated (log-fold change 1.93+-0.65)." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens WNT7B 7477 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "In IPF lung specimens, Wnt1, 7b, and 10b mRNA levels were markedly upregulated (log-fold change of 1.19+-0.43, 1.05+-0.43, And 1.58+-0.59, Respectively), whereas Wnt3a was significantly downregulated (log-fold change 1.93+-0.65)." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens WNT10B 7480 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "In IPF lung specimens, Wnt1, 7b, and 10b mRNA levels were markedly upregulated (log-fold change of 1.19+-0.43, 1.05+-0.43, And 1.58+-0.59, Respectively), whereas Wnt3a was significantly downregulated (log-fold change 1.93+-0.65)." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens WNT3A 89780 Gene mRNA down-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "In IPF lung specimens, Wnt1, 7b, and 10b mRNA levels were markedly upregulated (log-fold change of 1.19+-0.43, 1.05+-0.43, And 1.58+-0.59, Respectively), whereas Wnt3a was significantly downregulated (log-fold change 1.93+-0.65)." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens THY1 7070 Gene mRNA promoter hypomethylation NA NA qRT-PCR; MSP; MSPISH etc. no "In IPF samples in which Thy-1 expression is absent, the Thy-1 promoter region is methylated, whereas in lung samples retaining Thy-1 expression, the promoter region is unmethylated. Treatment with DNA methyltransferase inhibitors restores Thy-1 expression in Thy-1(-) fibroblasts." 18556592 Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Thy1 24832 Gene mRNA promoter hypomethylation NA NA qRT-PCR; MSP; MSPISH etc. no "In IPF samples in which Thy-1 expression is absent, the Thy-1 promoter region is methylated, whereas in lung samples retaining Thy-1 expression, the promoter region is unmethylated. Treatment with DNA methyltransferase inhibitors restores Thy-1 expression in Thy-1(-) fibroblasts." 18556592 Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis 2008 lung pulmonary_arterial_hypertension rattus_norvegicus Akt1 24185 Gene mRNA histone deacetylation NA NA Immunofluorescence; Immunoprecipitation assay etc. no "In PASMCs of PAH rats, Sodium butyrate (BU) counteracted platelet-derived growth factor (PDGF)-induced Ki67 expression, and arrested the cell cycle, mainly at G0 /G1 . BU decreased proliferating cell nuclear antigen, c-Myc and cyclin D1 transcription and protein expression, while increasing p21 expression. BU reduced the transcription of PDGF receptor-B, and that of Ednra and Ednrb, two major receptors in PAH progression. Wound healing, migration and pulmonary artery ring assays indicated that BU inhibited PDGF-induced PASMC migration. BU strongly inhibited PDGF-induced Akt phosphorylation, an effect reversed by the phosphatase inhibitor calyculin A. BU-treated cells showed a remarkable increase in acetylated Akt, indicating an inverse relationship between the levels of acetylated Akt and phospho-Akt." 23463962 Sodium butyrate inhibits platelet-derived growth factor-induced proliferation and migration in pulmonary artery smooth muscle cells through Akt inhibition 2013 lung idiopathic_pulmonary_fibrosis homo_sapiens NOX4 50507 Gene mRNA histone acetylation NA NA qRT-PCR; Immunoblot; Chromatin immunoprecipitation assay etc. no "In replicative senescent fibroblasts, the Nox4 gene is enriched with the activation histone mark, H4K16Ac, and inversely associated with the repressive histone mark, H4K20Me3, supporting an active transcriptional chromatin conformation. Silencing of the histone acetyltransferase Mof, which specifically acetylates H4K16, down-regulates Nox4 gene/protein expression." 25526894 Epigenetic mechanisms regulate NADPH oxidase-4 expression in cellular senescence 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens PLA2G2A 5320 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Pla2g2a 29692 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens PLA2G7 7941 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Pla2g7 301265 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGES 9536 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Ptges 59103 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens GPD1 2819 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Gpd1 60666 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Ingenuity pathway analysis classification revealed enrichment of several pathways and functional groups among common up-regulated genes. For instance, PLA2G2A/Pla2 g2a, phospholipase A2, group VII (PLA2G7/Pla2 g7), prostaglandin E synthase (PTGES/Ptges), and glycerol-3-phosphate dehydrogenase 1 (GPD1/Gpd1) are eicosanoid signaling components, suggesting that the dysregulation of this particular pathway is well conserved between the animal model and IPF, a finding of significant interest considering the phenotype of prostaglandin synthase 2 knockout mice. " 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung pulmonary_arterial_hypertension ovis_aries CCND1 100144763 Gene mRNA dna methylation NA NA qRT-PCR; LC/MS etc. no "Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII, accompanied by increased expression of p21 and reduced expression of CCND1. Apicidin inhibited serum-induced cell migration, and modulated profiling of expression of genes encoding pro-oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin." 24460719 Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells 2013 lung pulmonary_arterial_hypertension ovis_aries CCND1 100144763 Gene mRNA histone acetylation NA NA qRT-PCR; LC/MS etc. no "Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII, accompanied by increased expression of p21 and reduced expression of CCND1. Apicidin inhibited serum-induced cell migration, and modulated profiling of expression of genes encoding pro-oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin." 24460719 Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells 2013 lung pulmonary_arterial_hypertension ovis_aries CDKN1A 100302083 Gene mRNA histone acetylation NA NA qRT-PCR; LC/MS etc. no "Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII, accompanied by increased expression of p21 and reduced expression of CCND1. Apicidin inhibited serum-induced cell migration, and modulated profiling of expression of genes encoding pro-oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin." 24460719 Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells 2013 lung pulmonary_arterial_hypertension ovis_aries CDKN1A 100302083 Gene mRNA dna methylation NA NA qRT-PCR; LC/MS etc. no "Inhibition of class I and class II HDACs by apicidin and HDACi VIII suppressed proliferation of newborn PASMC and induced cell cycle arrest in G1 phase. Acetyl H3 levels were higher in newborn PASMC treated with apicidin and HDACi VIII, accompanied by increased expression of p21 and reduced expression of CCND1. Apicidin inhibited serum-induced cell migration, and modulated profiling of expression of genes encoding pro-oxidant and antioxidant enzymes. Contractility and global DNA methylation levels of newborn PASMCs were also markedly modulated by apicidin." 24460719 Role of histone deacetylases in regulation of phenotype of ovine newborn pulmonary arterial smooth muscle cells 2013 lung pulmonary_fibrosis rattus_norvegicus Acta2 81633 Gene mRNA dna methylation NA NA qRT-PCR; DNA methyltransferase assay; etc. no "Inhibition of DNA methyltransferase activity or knock down of DNA methyltransferase using specific small interfering RNA caused significant induction of alpha-SMA in fibroblasts. In contrast, induced overexpression of DNA methyltransferase suppressed alpha-SMA gene expression. Transforming growth factor beta induced myofibroblast differentiation was enhanced or suppressed by knockdown or overexpression of DNA methyltransferase, respectively. Finally, in vitro DNA methylation of the alpha-SMA promoter suppressed its activity. These findings suggest that DNA methylation mediated by DNA methyltransferase is an important mechanism regulating the alpha-SMA gene expression during myofibroblast differentiation." 20489138 Epigenetic regulation of myofibroblast differentiation by DNA methylation 2010 lung pulmonary_hypertension ovis_aries EHMT2 101115739 Gene mRNA histone methylation NA NA BrdU Incorporation Assay; qRT-PCR; etc. no "Inhibition of G9a by its inhibitor BIX-01294 reduced proliferation and contractility of foetal PASMCs and induced cell cycle arrest in G(1) phase,accompanied by increased p21 expression. Treatment of foetal PASMCs with BIX-01294 inhibited platelet-derived growth factor-induced cell proliferation and migration. Expression of calponin and ROCK-II proteins was reduced by BIX-01294 in a dose-dependent manner and BIX-01294 significantly increased global methylation level in the foetal PASMCs. Histone lysine methylation is involved in cell proliferation, migration, contractility and global DNA methylation in foetal PASMCs." 22691107 "BIX-01294 treatment blocks cell proliferation, migration and contractility in ovine foetal pulmonary arterial smooth muscle cells" 2012 lung pulmonary_hypertension rattus_norvegicus Edn1 24323 Gene mRNA histone acetylation NA NA ChIP assay; ET-1 expression in leucocytes; Isolation of peripheral blood leucocytes no "Intrauterine growth retardation (IUGR) can cause increased histone acetylation of the endothelin-1 (ET-1) gene from pulmonary vascular endothelial cells or the whole lung tissue and persist into later life,resulting in increased risk of pulmonary hypertension or asthma later in life. The ET-1 protein expression of leucocytes from the 1-week IUGR group was similar to that from the 1-week control group. ET-1 protein expression of leucocytes from 10-week IUGR rats was obviously higher than that of the other groups. The levels of acetylated histone H3 in the ET-1 promoter of leucocytes from the 1-week IUGR rats were significantly higher than those from the age-matched control group. Furthermore, the trends continued <=10 weeks after birth. In conclusion, epigenetic modifications of leucocytes can in part reflect the epigenetic changes of lung tissue in IUGR rats. Epigenetics of peripheral leucocytes may be used as a biomarker for predicting the risk of the development of disease, and may be used as a surrogate to investigate the subsequent development of pulmonary vascular disease or asthma." 27882215 Epigenetic changes in peripheral leucocytes as biomarkers in intrauterine growth retardation rat 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CDKN2B 1030 Gene mRNA dna methylation NA NA DNA methylation analysis; qRT-PCR; Immunoblot etc. no "IPF fibroblasts exhibit global differences in DNA methylation that may contribute to the excessive fibroproliferation associated with this disease. DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT) corresponded with differences in gene expression at the mRNA and protein level." 25215577 Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens CARD10 29775 Gene mRNA dna methylation NA NA DNA methylation analysis; qRT-PCR; Immunoblot etc. no "IPF fibroblasts exhibit global differences in DNA methylation that may contribute to the excessive fibroproliferation associated with this disease. DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT) corresponded with differences in gene expression at the mRNA and protein level." 25215577 Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens MGMT 4255 Gene mRNA dna methylation NA NA DNA methylation analysis; qRT-PCR; Immunoblot etc. no "IPF fibroblasts exhibit global differences in DNA methylation that may contribute to the excessive fibroproliferation associated with this disease. DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT) corresponded with differences in gene expression at the mRNA and protein level." 25215577 Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens CDKN2A 1029 Gene mRNA dna hypermethylation NA NA Genomic DNA digestion and promoter amplification; qRT-PCR; etc. no "IPF fibroblasts have reduced expression of the proapoptotic p14(ARF) attributable to promoter hypermethylation, wand the p14(ARF)-hypermethylated IPF fibroblasts were significantly more resistant to staurosporine-and S-nitrosoglutathione-induced apoptosis compared with normal and nonmethylated IPF fibroblasts (P < 0.01) And showed reduced levels of p53." 22707614 Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens CLDN5 7122 Gene mRNA dna methylation NA NA MSP; qRT-PCR; etc. no "IPF samples demonstrated higher DNA methyltransferase expression without observed alterations in global DNA methylation. Among the genes whose DNA methylation status and RNA expression were both significantly altered, 16 genes were hypermethylated in DNA associated with decreased mRNA expression or vice versa.Changes in DNA methylation correspond to altered mRNA expression of a number of genes, some with known and others with previously uncharacterized roles in IPF, suggesting that DNA methylation is important in the pathogenesis of IPF." 22700861 Altered DNA methylation profile in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens ZNF467 168544 Gene mRNA dna methylation NA NA MSP; qRT-PCR; etc. no "IPF samples demonstrated higher DNA methyltransferase expression without observed alterations in global DNA methylation. Among the genes whose DNA methylation status and RNA expression were both significantly altered, 16 genes were hypermethylated in DNA associated with decreased mRNA expression or vice versa.Changes in DNA methylation correspond to altered mRNA expression of a number of genes, some with known and others with previously uncharacterized roles in IPF, suggesting that DNA methylation is important in the pathogenesis of IPF." 22700861 Altered DNA methylation profile in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens TP53INP1 94241 Gene mRNA dna methylation NA NA MSP; qRT-PCR; etc. no "IPF samples demonstrated higher DNA methyltransferase expression without observed alterations in global DNA methylation. Among the genes whose DNA methylation status and RNA expression were both significantly altered, 16 genes were hypermethylated in DNA associated with decreased mRNA expression or vice versa.Changes in DNA methylation correspond to altered mRNA expression of a number of genes, some with known and others with previously uncharacterized roles in IPF, suggesting that DNA methylation is important in the pathogenesis of IPF." 22700861 Altered DNA methylation profile in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens DDAH1 23576 Gene mRNA dna methylation NA NA MSP; qRT-PCR; etc. no "IPF samples demonstrated higher DNA methyltransferase expression without observed alterations in global DNA methylation. Among the genes whose DNA methylation status and RNA expression were both significantly altered, 16 genes were hypermethylated in DNA associated with decreased mRNA expression or vice versa.Changes in DNA methylation correspond to altered mRNA expression of a number of genes, some with known and others with previously uncharacterized roles in IPF, suggesting that DNA methylation is important in the pathogenesis of IPF." 22700861 Altered DNA methylation profile in idiopathic pulmonary fibrosis 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens KCNJ2 3759 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; Statistical analysis etc. no KCNJ2 may be an indicator of the development of IPF and a surrogate marker for IPF differential diagnosis. 32184906 Upregulation of Potassium Voltage-Gated Channel Subfamily J Member 2 Levels in the Lungs of Patients with Idiopathic Pulmonary Fibrosis 2020 lung idiopathic_pulmonary_fibrosis homo_sapiens FGF7 2252 Gene mRNA up-regulation NA ERK-1 AND P38 MAP KINASE signaling pathway "Quantitative Analysis of KGF, JunB, and c-Jun mRNA; Statistical Analysis etc." no Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. 15677771 Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta 2005 lung idiopathic_pulmonary_fibrosis homo_sapiens LEF1 51176 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no Lef1 was significantly upregulated in IPF (log-fold change 0.85+-0.34). 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung silicosis mus_musculus Smad3 17127 Gene mRNA dysregulation Myd88; Smad3 NA qRT-PCR; Dual-luciferase reporter assay etc. no "Levels were reduced in both macrophages that were exposed to silica and fibroblasts that were exposed to TGF-B1. MiR-489 inhibited silica-induced pulmonary fibrosis primarily by repressing its target genes MyD88 and Smad3. Moreover, the up-regulated lncRNA cardiac hypertrophy-related factor (CHRF) reversed the inhibitory effect of miR-489 on MyD88 and Smad3 and then triggered the inflammation and fibrotic signaling pathways." 27506999 MiR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF 2016 lung silicosis mus_musculus Myd88 17874 Gene mRNA dysregulation Myd88; Smad3 NA qRT-PCR; Dual-luciferase reporter assay etc. no "Levels were reduced in both macrophages that were exposed to silica and fibroblasts that were exposed to TGF-B1. MiR-489 inhibited silica-induced pulmonary fibrosis primarily by repressing its target genes MyD88 and Smad3. Moreover, the up-regulated lncRNA cardiac hypertrophy-related factor (CHRF) reversed the inhibitory effect of miR-489 on MyD88 and Smad3 and then triggered the inflammation and fibrotic signaling pathways." 27506999 MiR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF 2016 lung respiratory_distress_syndrome_acute mus_musculus Thy1 21838 Gene mRNA down-regulation NA NA BAL; qRT-PCR; etc. no LincRNA-p21 expression was time-dependently increased and Thy-1 expression was time-dependently reduced in a mouse model of ARDS and in LPS-treated lung fibroblasts. LincRNA-p21 overexpression dramatically inhibited acetylation of H3 and H4 at the Thy-1 promoter and Thy-1 expression levels in HLF1 cells.LincRNA-p21 interference rescued LPS-induced increase of lung and BAL collagen contents. LincRNA-p21 could lead to pulmonary fibrosis in ARDS by inhibition of the expression of Thy-1. 27392907 Lipopolysaccharide promotes pulmonary fibrosis in acute respiratory distress syndrome (ARDS) via lincRNA-p21 induced inhibition of Thy-1 expression 2016 lung respiratory_distress_syndrome_acute mus_musculus Thy1 21838 Gene mRNA histone deacetylation NA NA BAL; qRT-PCR; etc. no LincRNA-p21 expression was time-dependently increased and Thy-1 expression was time-dependently reduced in a mouse model of ARDS and in LPS-treated lung fibroblasts. LincRNA-p21 overexpression dramatically inhibited acetylation of H3 and H4 at the Thy-1 promoter and Thy-1 expression levels in HLF1 cells.LincRNA-p21 interference rescued LPS-induced increase of lung and BAL collagen contents. LincRNA-p21 could lead to pulmonary fibrosis in ARDS by inhibition of the expression of Thy-1. 27392907 Lipopolysaccharide promotes pulmonary fibrosis in acute respiratory distress syndrome (ARDS) via lincRNA-p21 induced inhibition of Thy-1 expression 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGS2 5743 Gene mRNA histone hypermethylation NA NA qRT-PCR; ELISA etc. no "Marked increases in H3K9me3, H3K27me3, and DNA methylation, together with their respective modifying enzymes G9a, EZH2, and DNA methyltransferases (Dnmts) and respective binding proteins heterochromatin protein 1 (HP1), polycomb protein complex 1 (PRC1) and methyl CpG binding protein 2 (MeCP2), at the COX-2 promoter in lung fibroblasts from patients with IPF (F-IPFs) can induce COX-2 expression silence. G9a and EZH2 and the Dnmt1 inhibitor markedly reduced H3K9me3 (49-79%), H3K27me3 (44-81%), and DNA methylation (61-97%) at the COX-2 promoter. These reductions were correlated with increased histone H3 and H4 acetylation, resulting in COX-2 mRNA and protein reexpression in F-IPFs." 24652950 A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGS2 5743 Gene mRNA dna methylation NA NA qRT-PCR; ELISA etc. no "Marked increases in H3K9me3, H3K27me3, and DNA methylation, together with their respective modifying enzymes G9a, EZH2, and DNA methyltransferases (Dnmts) and respective binding proteins heterochromatin protein 1 (HP1), polycomb protein complex 1 (PRC1) and methyl CpG binding protein 2 (MeCP2), at the COX-2 promoter in lung fibroblasts from patients with IPF (F-IPFs) can induce COX-2 expression silence. G9a and EZH2 and the Dnmt1 inhibitor markedly reduced H3K9me3 (49-79%), H3K27me3 (44-81%), and DNA methylation (61-97%) at the COX-2 promoter. These reductions were correlated with increased histone H3 and H4 acetylation, resulting in COX-2 mRNA and protein reexpression in F-IPFs." 24652950 A central role for G9a and EZH2 in the epigenetic silencing of cyclooxygenase-2 in idiopathic pulmonary fibrosis 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Olr1 108078 Gene mRNA down-regulation Nlrp3 NA Dual-luciferase reporter assay; qRT-PCR; etc. no "Mechanistically, Let-7 was able to regulate the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) through binding to its 3'-UTR region. Forced expression of LOX1 promoted the expression of apoptosis-related protein and mtDNA damage markers via regulating NLRP3 which was also confirmed in BLM model mice under the combination therapy of the exosome and Let-7 inhibitor. Collectively, this study demonstrates that exosomal Let-7 from MenSCs remits pulmonary fibrosis through regulating ROS, mtDNA damage, and NLRP3 inflammasome activation. This provides a new approach of exocytosis on the treatment of fibrotic lung disease." 31949877 Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage 2019 lung idiopathic_pulmonary_fibrosis mus_musculus Nlrp3 216799 Gene mRNA down-regulation NA NA Dual-luciferase reporter assay; qRT-PCR; etc. no "Mechanistically, Let-7 was able to regulate the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX1) through binding to its 3'-UTR region. Forced expression of LOX1 promoted the expression of apoptosis-related protein and mtDNA damage markers via regulating NLRP3 which was also confirmed in BLM model mice under the combination therapy of the exosome and Let-7 inhibitor. Collectively, this study demonstrates that exosomal Let-7 from MenSCs remits pulmonary fibrosis through regulating ROS, mtDNA damage, and NLRP3 inflammasome activation. This provides a new approach of exocytosis on the treatment of fibrotic lung disease." 31949877 Exosomal miRNA Let-7 from Menstrual Blood-Derived Endometrial Stem Cells Alleviates Pulmonary Fibrosis through Regulating Mitochondrial DNA Damage 2019 lung pulmonary_hypertension rattus_norvegicus Mef2a 309957 Gene mRNA down-regulation Med13 MED13/NCOR1-MEF2 AXIS signaling pathway Animal model of RV failure; Cardiomyocytes isolation and culture etc. no "Mef2c expression was sharply increased in compensating phase of RVH tissues but was lost in decompensation phase of RVH. Myocardium-specific miR-208 was progressively downregulated as RV failure progressed. MiR-208 inhibition, as well as tumor necrosis factor-a, activates the MED13/NCoR1 axis, which in turn promotes Mef2 inhibition, closing a self-limiting feedback loop, driving the transition from compensating phase of RVH toward decompensation phase of RVH. In our model, serum tumor necrosis factor-a levels progressively increased with time while serum miR-208 levels decreased, mirroring its levels in RV myocardium." 25287062 A miR-208-Mef2 axis drives the decompensation of right ventricular function in pulmonary hypertension 2015 lung pulmonary_hypertension rattus_norvegicus Med13 303403 Gene mRNA down-regulation Med13 MED13/NCOR1-MEF2 AXIS signaling pathway Animal model of RV failure; Cardiomyocytes isolation and culture etc. no "Mef2c expression was sharply increased in compensating phase of RVH tissues but was lost in decompensation phase of RVH. Myocardium-specific miR-208 was progressively downregulated as RV failure progressed. MiR-208 inhibition, as well as tumor necrosis factor-a, activates the MED13/NCoR1 axis, which in turn promotes Mef2 inhibition, closing a self-limiting feedback loop, driving the transition from compensating phase of RVH toward decompensation phase of RVH. In our model, serum tumor necrosis factor-a levels progressively increased with time while serum miR-208 levels decreased, mirroring its levels in RV myocardium." 25287062 A miR-208-Mef2 axis drives the decompensation of right ventricular function in pulmonary hypertension 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Acta2 81633 Gene mRNA dna methylation NA NA Electrophoretic mobility shift assay; qRT-PCR; etc. no "Methyl CpG binding protein 2 (MeCP2) can bind to the methylated a-SMA gene. Suppression of MeCP2 gene expression caused significant reduction of a-SMA gene expression. In contrast, transient transfection of MeCP2 expression plasmid into fibroblasts enhanced a-SMA gene expression. MeCP2-deficient mice exhibited significantly decreased alveolar wall thickness, inflammatory cell infiltration, interstitial collagen deposition, and myofibroblast differentiation in response to endotracheal injection of bleomycin. Thus, MeCP2 is essential for myofibroblast differentiation and pulmonary fibrosis." 21435439 Essential role of MeCP2 in the regulation of myofibroblast differentiation during pulmonary fibrosis 2011 lung idiopathic_pulmonary_fibrosis mus_musculus Foxo3 56484 Gene mRNA down-regulation Foxo3a NA Mouse Lung Fibrosis Model; Human Lung Samples; Statistical Analysis etc. no "MicroRNA-29c (MiR-29c) expression is lower in AEC2s of individuals with idiopathic pulmonary fibrosis (IPF) than healthy lungs. Epithelial cells overexpressing miR-29c show higher proliferative rate and viability. MiR-29c protects epithelial cells from apoptosis by targeting Foxo3a. Both overexpression of miR-29c conventionally and AEC2s specifically leads to less fibrosis and better recovery in vivo. MiR-29c maintains epithelial integrity and promotes recovery from lung injury, thereby attenuating lung fibrosis in mice." 28799781 MicroRNA-29c Prevents Pulmonary Fibrosis by Regulating Epithelial Cell Renewal and Apoptosis 2017 lung idiopathic_pulmonary_fibrosis homo_sapiens SMURF2 64750 Gene mRNA up-regulation SMURF2 NA qRT-PCR; Dual-luciferase reporter assay; etc. no "Micrornas chips and real-time PCR confirmed in A549 EMT model has six, three cut micrornas, the expression level of miR - 424 through targeted Smurf2 enhance TGF - beta signaling pathways regulating muscle into fiber cell differentiation 6 up-regulated and 3 down-regulated miRNAs in a human lung epithelial cell EMT model were validated using miRNA microarray and real-time PCR. Up-regulated miR-424 regulates the myofibroblast differentiation during EMT by potentiating the TGF-B signaling pathway through Smurf2." 25524739 Regulation of myofibroblast differentiation by miR-424 during epithelial-to-mesenchymal transition 2014 lung pulmonary_fibrosis mus_musculus Taz 66825 Gene mRNA up-regulation NA NA Collection and Analysis of Expression Array Data; In situ hybridization etc. no "MiR-130/301 expression correlates with activation of YAP/TAZ, the PPARY-APOE-LRP8 axis, and matrix stiffening in pulmonary fibrosis and liver fibrosis. Forced miR-130/301 expression activates ECM remodeling and liver fibrosis in mice. Inhibition of the miR-130/301 family prevents ECM remodeling and disease progression in mouse models of pulmonary fibrosis and liver fibrosis. Mechanical forces act through a central feedback circuit between microRNA-130/301 and YAP/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states." 26667495 A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions 2015 lung pulmonary_fibrosis mus_musculus Yap1 22601 Gene mRNA up-regulation NA NA Collection and Analysis of Expression Array Data; In situ hybridization etc. no "MiR-130/301 expression correlates with activation of YAP/TAZ, the PPARY-APOE-LRP8 axis, and matrix stiffening in pulmonary fibrosis and liver fibrosis. Forced miR-130/301 expression activates ECM remodeling and liver fibrosis in mice. Inhibition of the miR-130/301 family prevents ECM remodeling and disease progression in mouse models of pulmonary fibrosis and liver fibrosis. Mechanical forces act through a central feedback circuit between microRNA-130/301 and YAP/TAZ to sustain a common fibrotic phenotype across a network of human physiologic and pathophysiologic states." 26667495 A YAP/TAZ-miR-130/301 molecular circuit exerts systems-level control of fibrosis in a network of human diseases and physiologic conditions 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens IGF1 3479 Gene mRNA down-regulation IGF-1 NA Dual-luciferase reporter assay; ELISA; qRT-PCR etc. no "MiR-130b-3p was downregulated in IPF lungs. MiR-130b-3p downregulation contributed to the activation of fibroblasts and the dysregulated epithelial-mesenchymal crosstalk by promoting IGF-1 secretion from lung epithelium, suggesting a key regulatory role for this miRNA in preventing lung fibrosis." 26953888 MiR-130b-3p Modulates Epithelial-Mesenchymal Crosstalk in Lung Fibrosis by Targeting IGF-1 2016 lung pulmonary_fibrosis homo_sapiens TGFBR1 7046 Gene mRNA dysregulation TGFBR1; TGFBR2 TGF-beta/SMAD signaling pathway qRT-PCR; Immunofluorescence etc. no "MiR-1343 reduces the expression of both TGF-B receptor 1 and 2 by directly targeting their 3'-UTRs. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. MiR-1343 may have direct therapeutic applications in fibrotic lung disease." 26542979 MiR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors 2016 lung pulmonary_fibrosis homo_sapiens TGFBR2 7048 Gene mRNA dysregulation TGFBR1; TGFBR2 TGF-beta/SMAD signaling pathway qRT-PCR; Immunofluorescence etc. no "MiR-1343 reduces the expression of both TGF-B receptor 1 and 2 by directly targeting their 3'-UTRs. As a result, the abundance of fibrotic markers is reduced, cell migration into a scratch wound impaired and epithelial-to-mesenchymal transition (EMT) repressed. Mature miR-1343 is readily detected in human neutrophils and HL-60 cells and is activated in response to stress in A549 lung epithelial cells. MiR-1343 may have direct therapeutic applications in fibrotic lung disease." 26542979 MiR-1343 attenuates pathways of fibrosis by targeting the TGF-beta receptors 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Tgfbr2 21813 Gene mRNA dysregulation Tgfbr2 NA Dual-luciferase reporter assay; qRT-PCR; etc. no MiR-153 expression was dysregulated in the lungs of mice with experimental pulmonary fibrosis and TGF-B1 decreased miR-153 expression in pulmonary fibroblasts. MiR-153 disturbs TGF-B1 signal transduction and its effects on fibroblast activation by post-transcriptional regulation of the expression of TGFBR2. 26216407 The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Nr1h3 22259 Gene mRNA dysregulation Lxra NA qRT-PCR; Oxysterol assay etc. no "MiR-155-/- mice developed exacerbated lung fibrosis, increased collagen deposition, collagen 1 and 3 mRNA expression, TGF-B production, and activation of alternatively activated macrophages, contributed by deregulation of the miR-155 target gene the liver X receptor (LXR)a in lung fibroblasts and macrophages.LXRa can increase the expression of Arginase 2, TGF-B, promote collagen production and IPF progression." 27746237 The role of microRNA-155/liver X receptor pathway in experimental and idiopathic pulmonary fibrosis 2016 lung pulmonary_hypertension rattus_norvegicus Cdkn1a 114851 Gene mRNA up-regulation P21 NA Immunohistochemistry; qRT-PCR; etc. no MiR-17 antagomir A-17 improves heart and lung function in experimental PH by interfering with lung vascular and right ventricular remodeling. The beneficial effects may be related to the up-regulation of p21. 22161164 Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension 2012 lung pulmonary_hypertension mus_musculus Cdkn1a 12575 Gene mRNA up-regulation P21 NA Immunohistochemistry; qRT-PCR; etc. no MiR-17 antagomir A-17 improves heart and lung function in experimental PH by interfering with lung vascular and right ventricular remodeling. The beneficial effects may be related to the up-regulation of p21. 22161164 Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension 2012 lung pulmonary_arterial_hypertension homo_sapiens PTPN11 5781 Gene mRNA down-regulation SHP2 STAT3-MIR-204-SRC-STAT3-NFAT signaling pathway TLDAS; qRT-PCR; Dual-luciferase reporter assay etc. no "MiR-204 expression in PASMCs is down-regulated in both human and rodent PAH. MiR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity." 21321078 Role for miR-204 in human pulmonary arterial hypertension 2011 lung pulmonary_arterial_hypertension rattus_norvegicus Ptpn11 25622 Gene mRNA down-regulation Shp2 STAT3-MIR-204-SRC-STAT3-NFAT signaling pathway? TLDAS; qRT-PCR; Dual-luciferase reporter assay etc. no "MiR-204 expression in PASMCs is down-regulated in both human and rodent PAH. MiR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity." 21321078 Role for miR-204 in human pulmonary arterial hypertension 2011 lung pulmonary_hypertension mus_musculus Notch3 18131 Gene mRNA down-regulation Notch3 NA Transfection of hPASMCs; qRT-PCR; etc. no "MiR-206 expression is reduced in hypoxia-induced PAH, correlated with an increase in right ventricular systolic pressure. Reduction of miR-206 levels in hPASMCs causes increased proliferation and reduced apoptosis and these effects were reversed by the overexpression of miR-206. MiR-206 overexpression down regulated Notch-3 expression." 23071643 Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation 2012 lung idiopathic_pulmonary_fibrosis mus_musculus Smad7 17131 Gene mRNA up-regulation Smad7 NA Northern Blot; qRT-PCR; Dual-luciferase reporter assay etc. no "MiR-21 is up-regulated in the lungs of mice with bleomycin-induced fibrosis and also in the lungs of patients with IPF, and was primarily localized to myofibroblasts. Administration of miR-21 antisense probes diminished the severity of experimental lung fibrosis in mice, even when treatment was started 5-7 d after initiation of pulmonary injury. TGF-Beta1 enhanced miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promoted, whereas knocking down miR-21 attenuated, the pro-fibrogenic activity of TGF-Beta1 in fibroblasts. A potential mechanism for the role of miR-21 in fibrosis is through regulating the expression of an inhibitory Smad, Smad7." 20643828 MiR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis 2010 lung idiopathic_pulmonary_fibrosis homo_sapiens SMAD7 4092 Gene mRNA up-regulation SMAD7 NA Northern Blot; qRT-PCR; Dual-luciferase reporter assay etc. no "MiR-21 is up-regulated in the lungs of mice with bleomycin-induced fibrosis and also in the lungs of patients with IPF, and was primarily localized to myofibroblasts. Administration of miR-21 antisense probes diminished the severity of experimental lung fibrosis in mice, even when treatment was started 5-7 d after initiation of pulmonary injury. TGF-Beta1 enhanced miR-21 expression in primary pulmonary fibroblasts. Increasing miR-21 levels promoted, whereas knocking down miR-21 attenuated, the pro-fibrogenic activity of TGF-Beta1 in fibroblasts. A potential mechanism for the role of miR-21 in fibrosis is through regulating the expression of an inhibitory Smad, Smad7." 20643828 MiR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis 2010 lung idiopathic_pulmonary_fibrosis mus_musculus Smad2 17126 Gene mRNA down-regulation Tbr1; Smad2 TGF-B signaling pathway qRT-PCR; Dual-luciferase reporter assay; etc. no MiR-27b was down-regulated in fibrotic lungs and fibroblasts from an experimental mouse model of pulmonary fibrosis. MiR-27b is an anti-fibrotic microRNA that inhibits fibroblast activation by targeting TGFB receptor 1 and SMAD2. 28095798 MiR-27b inhibits fibroblast activation via targeting TGFB signaling pathway 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Tgfbr1 21812 Gene mRNA down-regulation Tbr1; Smad2 TGF-B signaling pathway qRT-PCR; Dual-luciferase reporter assay; etc. no MiR-27b was down-regulated in fibrotic lungs and fibroblasts from an experimental mouse model of pulmonary fibrosis. MiR-27b is an anti-fibrotic microRNA that inhibits fibroblast activation by targeting TGFB receptor 1 and SMAD2. 28095798 MiR-27b inhibits fibroblast activation via targeting TGFB signaling pathway 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Dnm1l 74006 Gene mRNA hydroxymethylation Tet1 NA qRT-PCR; Dual-luciferase reporter assay; Masson's trichrome staining etc. no MiR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3'untranslated region to inhibit Drp-1 promoter hydroxymethylation and therefore inhibiting pulmonary fibrosis. 28294974 MiR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis 2017 lung idiopathic_pulmonary_fibrosis mus_musculus Tet1 52463 Gene mRNA hydroxymethylation Tet1 NA qRT-PCR; Dual-luciferase reporter assay; Masson's trichrome staining etc. no MiR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3'untranslated region to inhibit Drp-1 promoter hydroxymethylation and therefore inhibiting pulmonary fibrosis. 28294974 MiR-30a as Potential Therapeutics by Targeting TET1 through Regulation of Drp-1 Promoter Hydroxymethylation in Idiopathic Pulmonary Fibrosis 2017 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Dnm1l 114114 Gene mRNA down-regulation Drp-1 NA qRT-PCR; Immunofluorescence; etc. no "MiR-30a decreased in lung fibrosis; MiR-30a inhibited AECs-II apoptosis by repressing the mitochondrial fission dependent on Drp-1, and could function as a novel therapeutic target for lung fibrosis." 25284615 MiRNA-30a inhibits AECs-II apoptosis by blocking mitochondrial fission dependent on Drp-1 2014 lung cystic_fibrosis homo_sapiens CTSS 1520 Gene mRNA up-regulation IRF-1 MIR-31/IRF-1/CTSS signaling pathway ELISA; qRT-PCR etc. no "MiR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion." 24940638 MiR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production 2014 lung cystic_fibrosis homo_sapiens IRF1 3659 Gene mRNA up-regulation IRF-1 MIR-31/IRF-1/CTSS signaling pathway ELISA; qRT-PCR etc. no "MiR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion." 24940638 MiR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Tgfa 21802 Gene mRNA down-regulation Smad2; Tgfa NA Dual-luciferase reporter assay; PCR etc. no "MiR-323a-3p is downregulated in the epithelium of lungs with bronchiolitis obliterans syndrome (BOS) after lung transplantation, idiopathic pulmonary fibrosis (IPF), and murine bleomycin-induced fibrosis. MiR-323a-3p attenuates TGF-a and TGF-B signaling by directly targeting SMAD2 and TGFA. Moreover, miR-323a-3p lowers caspase-3 expression, thereby limiting programmed cell death from inducers of apoptosis and ER stress. Epithelial expression of miR-323a-3p modulates inhibitory crosstalk with fibroblasts. Downregulated expression of miR-323a-3p by the lung epithelium releases inhibition of various profibrotic pathways to promote fibroproliferation." 27942594 MiR-323a-3p regulates lung fibrosis by targeting multiple profibrotic pathways 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Smad2 17126 Gene mRNA down-regulation Smad2; Tgfa NA Dual-luciferase reporter assay; PCR etc. no "MiR-323a-3p is downregulated in the epithelium of lungs with bronchiolitis obliterans syndrome (BOS) after lung transplantation, idiopathic pulmonary fibrosis (IPF), and murine bleomycin-induced fibrosis. MiR-323a-3p attenuates TGF-a and TGF-B signaling by directly targeting SMAD2 and TGFA. Moreover, miR-323a-3p lowers caspase-3 expression, thereby limiting programmed cell death from inducers of apoptosis and ER stress. Epithelial expression of miR-323a-3p modulates inhibitory crosstalk with fibroblasts. Downregulated expression of miR-323a-3p by the lung epithelium releases inhibition of various profibrotic pathways to promote fibroproliferation." 27942594 MiR-323a-3p regulates lung fibrosis by targeting multiple profibrotic pathways 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Lpar1 14745 Gene mRNA down-regulation Lpa1; Smo NA qRT-PCR; Immunohistochemistry; etc. no "MiR-338*(miR-338-5p), which has been found to be associated with tumor progression, was down-regulated in fibroblasts and TGF-B-induced lung fibrotic tissues.LPA1 was proven to be a downstream target of miR-338*. MiR-338* attenuates the pathogenesis of pulmonary fibrosis through targeting LPA1. Thus, miR-338* can be a potential therapeutic target for the treatment of IPF." 27508041 MiR-338* suppresses fibrotic pathogenesis in pulmonary fibrosis through targeting LPA1 2016 lung pulmonary_fibrosis mus_musculus Bcl2 12043 Gene mRNA down-regulation Bcl2 NA Immunofluorescence; qRT-PCR etc. no MiR-449a expression was decreased in fibrotic lungs and activated fibroblasts. Autophagy was inhibited in fibrotic lung tissues and TGF-B1-treated fibroblasts. MiR-449a had an antifibrotic effect in silica-induced lung fibrosis. MiR-449a upregulated autophagic activity in vitro. Bcl2 is the autophagy-related target of miR-449a. TGF-B1 increase the expression of Bcl2 via the MAPK/ERK pathway. 27351886 MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens CCN4 8840 Gene mRNA up-regulation WISP1 NA qRT-PCR; Immunohistochemistry etc. no MiR-92a inhibt TGF-B1-induced WISP1 expression in pulmonary fibrosis. 24953558 MiR-92a regulates TGF-B1-induced WISP1 expression in pulmonary fibrosis 2014 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Stat3 25125 Gene mRNA dysregulation Stat3 NA Immunofluorescence; qRT-PCR etc. no "MiR-98 decreased in the fibrotic lung tissues, while its target gene Stat3 was activated with PF development and the expression of Stat3 and p-Stat3 was significantly increased in BLM-induced PF. Arsenic trioxide prevented rat PF by up-regulation of miR-98 and inhibition of its downstream Stat3 signals." 25123535 Arsenic trioxide prevents rat pulmonary fibrosis via miR-98 overexpression 2014 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP3 4314 Gene mRNA up-regulation NA NA Immunohistochemistry; Blood biomarker levels of MMP3; CXCL13 in a separate cohort of IPF patients etc. no MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF. 25217476 Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL13 10563 Gene mRNA up-regulation NA NA Immunohistochemistry; Blood biomarker levels of MMP3; CXCL13 in a separate cohort of IPF patients etc. no MMP3 and CXCL13 are systemic biomarkers that reflect the aggregate burden of these pathological features across total lung tissue. These biomarkers may have clinical utility as prognostic and/or surrogate biomarkers of disease activity in interventional studies in IPF. 25217476 Heterogeneous gene expression signatures correspond to distinct lung pathologies and biomarkers of disease severity in idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP7 4316 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no MMP7 was previously shown to be a regulator and potentially predictive protein plasma biomarker in IPF. 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Mmp7 25335 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no MMP7 was previously shown to be a regulator and potentially predictive protein plasma biomarker in IPF. 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Col1a1 12842 Gene mRNA interact with miRNA Sgca; Hils1; Ppp1r9b; Samd14; Pdk2; Itga3 NA qPCR; Knockdown etc. no "Moreover, H19 interacted with miR-29b through directly binding to the 3'UTR; miR-29b inhibited COL1A1 expression by directly binding to the 4'UTR." 27613097 The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis 2016 lung idiopathic_pulmonary_fibrosis mus_musculus Acta2 11475 Gene mRNA interact with miRNA Ankrd22; Stambpl1; Fas NA qPCR; Knockdown etc. no "Moreover, H19 interacted with miR-29b through directly binding to the 3'UTR; miR-29b inhibited COL1A1 expression by directly binding to the 5'UTR." 27613097 The effect of H19-miR-29b interaction on bleomycin-induced mouse model of idiopathic pulmonary fibrosis 2016 lung pulmonary_fibrosis mus_musculus Ifng 15978 Gene mRNA dysregulation NA NA Masson's trichrome staining; LUMA; qRT-PCR etc. no "MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. Alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development." 26375518 Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure 2016 lung pulmonary_fibrosis mus_musculus Tnf 21926 Gene mRNA dysregulation NA NA Masson's trichrome staining; LUMA; qRT-PCR etc. no "MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. Alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development." 26375518 Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure 2016 lung pulmonary_fibrosis mus_musculus Thy1 21838 Gene mRNA dysregulation NA NA Masson's trichrome staining; LUMA; qRT-PCR etc. no "MWCNT lead to DNA hypomethylation in the lung and blood, which coincided with disease development. Alterations in gene-specific methylation correspond with an inflammatory response to MWCNT exposure. In addition, global DNA methylation in the lung and blood coincides with MWCNT-induced disease development, suggesting its potential as a biomarker of both exposure and disease development." 26375518 Alterations in DNA methylation corresponding with lung inflammation and as a biomarker for disease development after MWCNT exposure 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens FN1 2335 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR etc. no "Next, we analyzed the expression of the well-characterized Wnt target genes fibronectin (Fn) 1, matrix metalloproteinase (Mmp) 7, and cyclin D1 in IPF lungs. As depicted in Figure 7b, all of these Wnt target genes were upregulated in IPF lung samples, as compared with transplant donor samples." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP7 4316 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR etc. no "Next, we analyzed the expression of the well-characterized Wnt target genes fibronectin (Fn) 1, matrix metalloproteinase (Mmp) 7, and cyclin D1 in IPF lungs. As depicted in Figure 7b, all of these Wnt target genes were upregulated in IPF lung samples, as compared with transplant donor samples." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens CCND1 595 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR etc. no "Next, we analyzed the expression of the well-characterized Wnt target genes fibronectin (Fn) 1, matrix metalloproteinase (Mmp) 7, and cyclin D1 in IPF lungs. As depicted in Figure 7b, all of these Wnt target genes were upregulated in IPF lung samples, as compared with transplant donor samples." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens CCNA2 890 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; etc. no "One of the remarkable features of our study is the localization of increased CCNA2 expression to the alveolar epithelium, rather than to fibroblasts or myofibroblastic foci. CCNA2 is the main A-type cyclin present in somatic cells (36) and a mediator of the cell cycle. The overexpression and localization of CCNA2 to epithelial cells but not to mesenchymal cells suggests that IPF-AEx is probably an extension of the epithelial injury and dysregulation that characterizes IPF (37) and definitely is not a result of uncontrolled fibroblast proliferation." 19363140 Gene expression profiles of acute exacerbations of idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL13 6357 Gene mRNA up-regulation IGF-I NA qRT-PCR; Immunohistochemistry; Bleomycin exposure etc. no "Our gene expression profiling study identified several chemokines (CCL13, CXCL12, and CXCL14) and growth factors and their receptors (insulin-like growth factor-I [IGF-I], IGF-I-binding protein-5, and platelet-derived growth factor receptor-like) to be overexpressed in the lung specimens obtained from patients with IIP." 16998095 Gene expression profiling of familial and sporadic interstitial pneumonia 2007 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL14 9547 Gene mRNA up-regulation NA NA qRT-PCR; Immunohistochemistry; Bleomycin exposure etc. no "Our gene expression profiling study identified several chemokines (CCL13, CXCL12, and CXCL14) and growth factors and their receptors (insulin-like growth factor-I [IGF-I], IGF-I-binding protein-7, and platelet-derived growth factor receptor-like) to be overexpressed in the lung specimens obtained from patients with IIP." 16998095 Gene expression profiling of familial and sporadic interstitial pneumonia 2007 lung pulmonary_fibrosis mus_musculus Id2 15902 Gene mRNA up-regulation NA NA Dual-luciferase reporter assay; Masson's trichrome staining; qRT-PCR etc. no Overexpression of Id2 in primary AECs promotes proliferation by inhibiting a retinoblastoma protein/c-Abl interaction leading to greater c-Abl activity. Id2 also blocks transforming growth factor B1-mediated expression of type I collagen by inhibiting Twist. Histone deacetylase inhibitors induce Id2 expression by adult AECs. 25661109 Overexpression of inhibitor of DNA-binding 2 attenuates pulmonary fibrosis through regulation of c-Abl and Twist 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Sirt1 93759 Gene mRNA up-regulation Sirt1 NA Immunohistochemistry; H&E etc. no "P53 and apoptosis is induced with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients and in mice with lung injury. Treatment with the caveolin-1 scaffolding domain peptide (CSP) reversed these effects. AECs from IPF lungs or mice with diverse types of lung injuries showed increased p53 acetylation and miR-34a expression with reduction in Sirt1. Bleomycin failed to induce miR-34a in p53- or plasminogen activator inhibitor-1 (PAI-1)-deficient mice. CSP-mediated inhibition of miR-34a restored Sirt1, suppressed p53 acetylation and apoptosis in injured AECs, and prevented pulmonary fibrosis (PF). AEC-specific suppression of miR-34a inhibited bleomycin-induced p53, PAI-1, and apoptosis and prevented PF, whereas overexpression of precursor-miR-34a increased p53, PAI-1, and apoptosis in AECs of mice unexposed to bleomycin. P53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis." 28273432 P53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis 2017 lung idiopathic_pulmonary_fibrosis mus_musculus Trp53 22059 Gene mRNA up-regulation Sirt1 NA Immunohistochemistry; H&E etc. no "P53 and apoptosis is induced with suppression of urokinase-type plasminogen activator (uPA) and the uPA receptor in AECs from the lungs of IPF patients and in mice with lung injury. Treatment with the caveolin-1 scaffolding domain peptide (CSP) reversed these effects. AECs from IPF lungs or mice with diverse types of lung injuries showed increased p53 acetylation and miR-34a expression with reduction in Sirt1. Bleomycin failed to induce miR-34a in p53- or plasminogen activator inhibitor-1 (PAI-1)-deficient mice. CSP-mediated inhibition of miR-34a restored Sirt1, suppressed p53 acetylation and apoptosis in injured AECs, and prevented pulmonary fibrosis (PF). AEC-specific suppression of miR-34a inhibited bleomycin-induced p53, PAI-1, and apoptosis and prevented PF, whereas overexpression of precursor-miR-34a increased p53, PAI-1, and apoptosis in AECs of mice unexposed to bleomycin. P53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis." 28273432 P53 and miR-34a Feedback Promotes Lung Epithelial Injury and Pulmonary Fibrosis 2017 lung Pulmonary_Disease_Chronic_Obstructive homo_sapiens CXCL8 3576 Gene mRNA histone hyperacetylation NA NA qRT-PCR; HDAC activity assay etc. no Patients with COPD have a progressive reduction in total HDAC activity that reflects the severity of the disease; Specimens of lung tissue obtained from patients with increasing clinical stages of COPD had graded reductions in HDAC activity and increases in interleukin-8 messenger RNA (mRNA) and histone-4 acetylation at the interleukin-8 promoter. 15888697 Decreased histone deacetylase activity in chronic obstructive pulmonary disease 2005 lung idiopathic_pulmonary_fibrosis homo_sapiens POSTN 10631 Gene mRNA up-regulation NA NA BALF; Immunohistochemistry; ELISA etc. no "Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias." 21177844 "Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias" 2011 lung pulmonary_hypertension mus_musculus Hif1a 15251 Gene mRNA down-regulation Hif-1a NA Dual-luciferase reporter assay; qRT-PCR; etc. no "Placenta growth factor(PlGF) treatment of endothelial cells resulted in reduced levels of miR-199a2, which targeted the 3'-UTR of HIF-1a mRNA and concomitantly led to augmented ET-1 expression. Fenofibrate, a PPARa agonist, increased the expression of miR-199a2, which was responsible for reduced expression of HIF-1a and ET-1. In vivo studies of fenofibrate-fed Berkeley sickle mice resulted in increased levels of miR-199a2 and reduced levels of ET-1 in lung tissues. Fenofibrate-induced miR-199a2 expression can ameliorate PH by reduction of ET-1 levels." 25389292 Peroxisome proliferator-activated receptor-a-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1a 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Parp1 11545 Gene mRNA dna methylation NA NA qPCR; PARP assay etc. no "Poly(ADP-ribosyl)ation (PARylation) is a post-translational protein modification effected by enzymes belonging to the poly(ADP-ribose) polymerase (PARP) superfamily, mainly by PARP-1. Overexpression of PARP-1activated expression of the a-SMA gene (Acta2) in lung fibroblasts. Suppression of PARP-1 activity or gene expression had the opposite effect on these cells. PARP-1-deficient cells also had reduced a-SMA gene expression. PARP-1 can affect the binding of smad3 to a-SMA promoter by inhibiting DNA methylation of a-SMA gene. PARP activity in lung fibroblasts isolated from idiopathic pulmonary fibrosis patients was significantly higher than that in cells isolated from control subjects. PARP-1-deficient mice exhibited reduced pulmonary fibrosis in response to bleomycin-induced lung injury." 23260200 Regulation of myofibroblast differentiation by poly(ADP-ribose) polymerase 1 2013 lung idiopathic_pulmonary_fibrosis homo_sapiens FOXJ1 2302 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "Recursive feature elimination using gene expression values identified FOXJ1, NELL2, SCGB3A1, LRRC34 and MYL3 as the top five most predictive genes (Fig 8D)." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LRRC34 151827 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "Recursive feature elimination using gene expression values identified FOXJ1, NELL2, SCGB3A1, LRRC34 and MYL3 as the top five most predictive genes (Fig 8D)." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MYL3 4634 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "Recursive feature elimination using gene expression values identified FOXJ1, NELL2, SCGB3A1, LRRC34 and MYL3 as the top five most predictive genes (Fig 8D)." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens NELL2 4753 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "Recursive feature elimination using gene expression values identified FOXJ1, NELL2, SCGB3A1, LRRC34 and MYL3 as the top five most predictive genes (Fig 8D)." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SCGB3A1 92304 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "Recursive feature elimination using gene expression values identified FOXJ1, NELL2, SCGB3A1, LRRC34 and MYL3 as the top five most predictive genes (Fig 8D)." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LCN2 3934 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Remarkably, similar expression change intensities were found for several common differentially expressed genes in both species (Figure 2, Tables 2 and and3),3), such as matrix metallopeptidase 7 (MMP7/Mmp7; 9.2-fold in IPF, 21.1-fold in bleomycin), the phospholipase A2, group 2A (PLA2G2A/Pla2 g2a; 7.8-fold in IPF, 4.3-fold in bleomycin), lipocalin-2 (LCN2/Lcn2 4.6-fold in IPF, 3.5-fold in bleomycin), collagen triple helix repeat containing 1 (CTHRC1/Cthrc1; 4.3-fold in IPF, 3.2-fold in bleomycin), and complement component 6 (C6; 3.7-fold in IPF, 6.5-fold in bleomycin)." 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Lcn2 170496 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Remarkably, similar expression change intensities were found for several common differentially expressed genes in both species (Figure 2, Tables 2 and and3),3), such as matrix metallopeptidase 7 (MMP7/Mmp7; 9.2-fold in IPF, 21.1-fold in bleomycin), the phospholipase A2, group 2A (PLA2G2A/Pla2 g2a; 7.8-fold in IPF, 4.3-fold in bleomycin), lipocalin-2 (LCN2/Lcn2 4.6-fold in IPF, 3.5-fold in bleomycin), collagen triple helix repeat containing 1 (CTHRC1/Cthrc1; 4.3-fold in IPF, 3.2-fold in bleomycin), and complement component 6 (C6; 3.7-fold in IPF, 6.5-fold in bleomycin)." 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens C6 729 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Remarkably, similar expression change intensities were found for several common differentially expressed genes in both species (Figure 2, Tables 2 and and3),3), such as matrix metallopeptidase 7 (MMP7/Mmp7; 9.2-fold in IPF, 21.1-fold in bleomycin), the phospholipase A2, group 2A (PLA2G2A/Pla2 g2a; 7.8-fold in IPF, 4.3-fold in bleomycin), lipocalin-2 (LCN2/Lcn2 4.6-fold in IPF, 3.5-fold in bleomycin), collagen triple helix repeat containing 1 (CTHRC1/Cthrc1; 4.3-fold in IPF, 3.2-fold in bleomycin), and complement component 6 (C6; 3.7-fold in IPF, 6.5-fold in bleomycin)." 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis rattus_norvegicus C6 24237 Gene mRNA up-regulation NA NA Cell Culture; Microarray Statistical Data Analysis; Gene Expression Analysis no "Remarkably, similar expression change intensities were found for several common differentially expressed genes in both species (Figure 2, Tables 2 and and3),3), such as matrix metallopeptidase 7 (MMP7/Mmp7; 9.2-fold in IPF, 21.1-fold in bleomycin), the phospholipase A2, group 2A (PLA2G2A/Pla2 g2a; 7.8-fold in IPF, 4.3-fold in bleomycin), lipocalin-2 (LCN2/Lcn2 4.6-fold in IPF, 3.5-fold in bleomycin), collagen triple helix repeat containing 1 (CTHRC1/Cthrc1; 4.3-fold in IPF, 3.2-fold in bleomycin), and complement component 6 (C6; 3.7-fold in IPF, 6.5-fold in bleomycin)." 25029475 A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens ROR2 4920 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway qRT-PCR; ELISA etc. no "ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF." 32951408 Upregulation of receptor tyrosine kinase-like orphan receptor 2 in idiopathic pulmonary fibrosis 2020 lung idiopathic_pulmonary_fibrosis homo_sapiens S100A4 6275 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; Immunofluorescence etc. no "S100A4 is expressed by alpha-SMA-positive cells in the interstitium of the IPF patients. S100A4 may participate in the development of IPF, and its protein level may be a candidate diagnostic and therapeutic marker for IPF." 32755764 The S100 calcium-binding protein A4 level is elevated in the lungs of patients with idiopathic pulmonary fibrosis 2020 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Smad7 81516 Gene mRNA histone deacetylation NA NA Masson's trichrome staining; Immunohistochemistry; Immunofluorescence etc. no "SAHA (histone deacetylase inhibitor, HDACi) suppressed PQ-induced lung fibrosis in rats by stabilizing Smad7 level via preventing Smad7 from deacetylation, thus attenuating Smad3 activity, resulting in the inhibition of fibroblast differentiation and collagen expression." 27747000 Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing Smad7 from deacetylation in rats 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens IGFBP2 3485 Gene mRNA up-regulation NA IGF SIGNALLING PATHWAY Biomarkers measurements in serum; Pulmonary function tests; Statistical analysis etc. no Serum IGFBP-1 and -2 are increased in idiopathic pulmonary fibrosis and IGFBP-2 may be reduced by anti-fibrosing therapy. IGFBPs may be promising biomarkers in IPF. 27215343 Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens IGFBP1 3484 Gene mRNA up-regulation NA IGF SIGNALLING PATHWAY Biomarkers measurements in serum; Pulmonary function tests; Statistical analysis etc. no Serum IGFBP-1 and -2 are increased in idiopathic pulmonary fibrosis and IGFBP-2 may be reduced by anti-fibrosing therapy. IGFBPs may be promising biomarkers in IPF. 27215343 Raised serum levels of IGFBP-1 and IGFBP-2 in idiopathic pulmonary fibrosis 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens SFTPD 6441 Gene mRNA up-regulation NA NA "Change in FVC and DLco, and definition of deterioration; Changes in SP-A, SP-D, and KL-6; Statistical analysis etc." no "Serum levels of SP-A, SP-D, and KL-6 have been shown to be useful in predicting prognosis and monitoring disease activity in patients with IPF." 32005219 Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis 2020 lung idiopathic_pulmonary_fibrosis homo_sapiens MUC1 4582 Gene mRNA up-regulation NA NA "Change in FVC and DLco, and definition of deterioration; Changes in SP-A, SP-D, and KL-6; Statistical analysis etc." no "Serum levels of SP-A, SP-D, and KL-6 have been shown to be useful in predicting prognosis and monitoring disease activity in patients with IPF." 32005219 Surfactant protein A as a biomarker of outcomes of anti-fibrotic drug therapy in patients with idiopathic pulmonary fibrosis 2020 lung idiopathic_pulmonary_fibrosis homo_sapiens SFRP2 6423 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway qRT-PCR; Immunohistochemistry; Bleomycin exposure etc. no SFRP2 is almost fourfold upregulated in the diseased tissue. 16998095 Gene expression profiling of familial and sporadic interstitial pneumonia 2007 lung idiopathic_pulmonary_fibrosis homo_sapiens THY1 7070 Gene mRNA dna?hypermethylation NA NA qRT-PCR; Immunohistochemistry etc. no "Significant global hypermethylation was detected in hypoxic fibroblasts relative to normoxic controls and was accompanied by increased expression of myofibroblast markers. Thy-1 mRNA expression was suppressed in hypoxic cells, which was restored with the demethylating agent 5-aza-2'-deoxycytidine." 22938014 Hypoxia-induced DNA hypermethylation in human pulmonary fibroblasts is associated with Thy-1 promoter methylation and the development of a pro-fibrotic phenotype 2012 lung pulmonary_fibrosis homo_sapiens SMAD3 4088 Gene mRNA dna hypomethylation NA NA PCR; ELISA; Mass spectrometry etc. no "Smad3 gene hypomethylation might promote pulmonary fibrosis in Uygur PBL patients via increased Smad3 mRNA expression. Smad3 methylation, Smad3 mRNA expression and TGF-B level were correlated with the number of pigeons bred by patients." 28562330 The correlation between pulmonary fibrosis and methylation of peripheral Smad3 in cases of pigeon breeder's lung in a Chinese Uygur population 2017 lung pulmonary_hypertension rattus_norvegicus Sod2 24787 Gene mRNA dna methylation NA NA EPR; Amplex red; Immunofluorescence etc. no "SOD2 expression in PASMCs is decreased in PAH patients and fawn-hooded rats (FHRs) with PAH.Genomic bisulfite sequencing demonstrates selective hypermethylation of a CpG island in an enhancer region of intron 2 and another in the promoter. Differential methylation occurs selectively in PAs versus aortic SMCs and is reversed by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, restoring both SOD2 expression and the ratio of proliferation to apoptosis. Expression of the enzymes that mediate gene methylation, DNA methyltransferases 1 and 3B, is upregulated in FHR lungs. Tissue-specific, epigenetic SOD2 deficiency initiates and sustains a heritable form of PAH by impairing redox signaling and creating a proliferative, apoptosis-resistant PASMC. SOD augmentation regresses experimental PAH." 20529999 Epigenetic attenuation of mitochondrial superoxide dismutase 2 in pulmonary arterial hypertension: a basis for excessive cell proliferation and a new therapeutic target 2010 lung idiopathic_pulmonary_fibrosis homo_sapiens SRF 6722 Gene mRNA up-regulation NA NA Data compilation; Statistical analysis etc. no "SRF is a transcription factor that is activated by the p38 MAP kinase pathway [24] and by increased extracellular matrix stiffness through mechanotransduction [25]. SRF is essential for collagen-1 expression by lung fibroblasts in vitro [26], while inhibition of the SRF pathway by the small molecule CCG-203971 attenuates lung fibrogenesis in the bleomycin-induced lung fibrosis model in mice [27]. Interestingly, SRF drives CTGF expression in fibroblasts [28], raising the hypothesis that the stable overexpression of the SRF/CTGF axis may contribute to the heritable profibrotic phenotype of lung fibroblasts in IPF." 27983601 Transcriptome of Cultured Lung Fibroblasts in Idiopathic Pulmonary Fibrosis: Meta-Analysis of Publically Available Microarray Datasets Reveals Repression of Inflammation and Immunity Pathways 2016 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Lpar1 116744 Gene mRNA up-regulation Lpa1 NA qRT-PCR; Mtt assay; etc. no "Tectorigenin inhibits the proliferation of pulmonary fibroblasts in vitro and enhances miR-338* expression, which might in turn downregulate LPA1. This indicates a potential inhibitory role of tectorigenin on the pathogenesis of IPF" 20600766 Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis 2010 lung idiopathic_pulmonary_fibrosis mus_musculus Thy1 21838 Gene mRNA dna methylation NA NA qRT-PCR; DNMT Activity Assay etc. no "TGF-B1 epigenetically regulates lung fibroblast phenotype through methylation of the Thy-1 promoter. Targeted inhibition of DNMT t might prevent fibroblast to myofibroblast transdifferentiation and collagen deposition, which in turn could prevent fibrogenesis in the lung and other organs." 26333597 TGF-B1 epigenetically modifies Thy-1 expression in primary lung fibroblasts 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL12 6387 Gene mRNA up-regulation CXCR4 NA qRT-PCR; Immunohistochemistry; Bleomycin exposure etc. no "The chemokine CXCL12, or stromal cell-derived factor 1 (SDF-1), is an important regulator of hematopoietic cell development, migration, and proliferation, and is the only known ligand for the CXCR4 receptor." 16998095 Gene expression profiling of familial and sporadic interstitial pneumonia 2007 lung cystic_fibrosis homo_sapiens CFTR 1080 Gene mRNA up-regulation CFTR NA Dual-luciferase reporter assay; qRT-PCR; In situ Hybridization etc. no The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis; Chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients. 23226399 MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung 2012 lung cystic_fibrosis mus_musculus Cftr 12638 Gene mRNA up-regulation Cftr NA Dual-luciferase reporter assay; qRT-PCR; In situ Hybridization etc. no The Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is a chloride channel that plays a critical role in the lung by maintaining fluid homeostasis. Absence or malfunction of CFTR leads to Cystic Fibrosis; Chronic cigarette smoking up-regulates miR-101 and that this miRNA could contribute to suppression of CFTR in the lungs of COPD patients. 23226399 MiR-101 and miR-144 regulate the expression of the CFTR chloride channel in the lung 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens PTGER2 5732 Gene mRNA dna hypermethylation NA PTEN-AKT signaling pathway Global DNA methylation assay; qRT-PCR; Immunoblot etc. no The down-regulation of PTGER2 and consequent PGE2 resistance are both mediated by DNA hypermethylation; Increased Akt signal transduction as a novel mechanism that promotes DNA hypermethylation during fibrogenesis. 20889571 Hypermethylation of PTGER2 confers prostaglandin E2 resistance in fibrotic fibroblasts from humansand mice 2010 lung idiopathic_pulmonary_fibrosis mus_musculus Ptger2 19217 Gene mRNA dna hypermethylation NA PTEN-AKT signaling pathway Global DNA methylation assay; qRT-PCR; Immunoblot etc. no The down-regulation of PTGER2 and consequent PGE2 resistance are both mediated by DNA hypermethylation; Increased Akt signal transduction as a novel mechanism that promotes DNA hypermethylation during fibrogenesis. 20889571 Hypermethylation of PTGER2 confers prostaglandin E2 resistance in fibrotic fibroblasts from humansand mice 2010 lung idiopathic_pulmonary_fibrosis mus_musculus Hmga2 15364 Gene mRNA down-regulation Hmga2 NA Mtt assay; qRT-PCR; etc. no The expression of miR 221 was inhibited in both IPF tissues and pulmonary cells whereas mRNA and protein expression of HMGA2 were increased. MiR 221 targets HMGA2 to inhibit BLM induced pulmonary fibrosis through the TGF B1/Smad3 signaling pathway. 27513632 MiR 221 targets HMGA2 to inhibit bleomycin induced pulmonary fibrosis by regulating TGF B1/Smad3-induced EMT 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens AGTR1 185 Gene mRNA up-regulation NA MKK1/MKK2 SIGNALLING PATHWAY qRT-PCR; Immunohistochemistry etc. no The finding that AGTR1 localizes to fibroblastic foci in IPF biopsies supports the potential relevance of the angiotensin system in this disease and suggests that the pro-fibrotic role of AGTR1 in IPF is not limited to epithelial cells [31]. Further studies are needed to assess the functional effects of AGTR1 stimulation in lung fibroblasts and to evaluate the biological role of AGTR1 in lung fibrosis. 15571627 Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblasts 2004 lung idiopathic_pulmonary_fibrosis homo_sapiens IL33 90865 Gene mRNA up-regulation NA NA ELISA; Statistical analysis etc. no The IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases. 28202030 Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis 2017 lung idiopathic_pulmonary_fibrosis homo_sapiens TSLP 85480 Gene mRNA up-regulation NA NA ELISA; Statistical analysis etc. no The IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases. 28202030 Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis 2017 lung Familial_Persistent_Pulmonary_Hypertension_of_the_Newborn rattus_norvegicus Nos3 24600 Gene mRNA histone acetylation NA NA qRT-PCR; Immunohistochemistry etc. no The levels of acetylated histone H3 and acetylated histone H4 at the proximal promoter of the eNOS gene in pulmonary vascular endothelial cells from Persistent pulmonary hypertension of the newborn (PPHN) were significantly higher than those from the control group. These changes of epigenetic modifications at the eNOS gene promoter were consistent with increased levels of eNOS mRNA and protein in PPHN. 20724942 Epigenetic regulation of the endothelial nitric oxide synthase gene in persistent pulmonary hypertension of the newborn rat 2010 lung pulmonary_arterial_hypertension rattus_norvegicus Edn1 24323 Gene mRNA histone acetylation NA NA Immunohistochemistry; qRT-PCR etc. no "The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1a (HIF-1a) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling." 23406533 Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR 2013 lung idiopathic_pulmonary_fibrosis mus_musculus Ptpa 110854 Gene mRNA down-regulation NA PP2A/HISTONE DEACETYLASE C4/MICRORNA-29 signaling pathway qRT-PCR; Immunohistochemistry etc. no "The mechanism for suppression of miR-29 during IPF fibroblast interaction with polymerized collagen involves inappropriately low protein phosphatase (PP) 2A function, leading to histone deacetylase (HDA) C4 phosphorylation and decreased nuclear translocation of HDAC4.PF fibroblast interaction with polymerized type I collagen results in an aberrant PP2A/HDAC4 axis, which suppresses miR-29, causing a pathologic increase in type I collagen expression." 25612003 Pathologic Regulation of Collagen I by an Aberrant Protein Phosphatase 2A/Histone Deacetylase C4/MicroRNA-29 Signal Axis in Idiopathic Pulmonary Fibrosis Fibroblasts 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens XCL1 6375 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL17 6361 Gene mRNA up-regulation CCR4 NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL5 6352 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL9 4283 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL10 3627 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL11 6373 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL15 6359 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL1 2919 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL6 6372 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL7 6354 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL17 284340 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL13 10563 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCL14 6358 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL14 9547 Gene mRNA up-regulation NA NA "Identification of gene-expression subsets, principal component analysis and differential gene expression; Determination of ligand-receptor interactions using single cell RNA datasets; Development of pirfenidone response signature" no "The Myeloid-enriched IPF subset (Subset 1) had increased expression of XCL1, CCL17, CCL5, CXCL9, CXCL10 and CXCL11, whereas the Ciliated epithelium-enriched IPF subset (Subset 2) had increased expression of CCL15, CXCL1, CXCL6, CCL7, CXCL17, CXCL13, CCL14 and CXCL14." 33755690 Lung gene expression and single cell analyses reveal two subsets of idiopathic pulmonary fibrosis (IPF) patients associated with different pathogenic mechanisms 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TFPI 7035 Gene mRNA up-regulation NA NA ELISA; Immunohistochemistry etc. no The TF and TFPI levels in BAL fluid supernatant were significantly higher in IPF patients than in normal controls. 10946084 Relevance of tissue factor and tissue factor pathway inhibitor for hypercoagulable state in the lungs of patients with idiopathic pulmonary fibrosis 2000 lung idiopathic_pulmonary_fibrosis mus_musculus Thy1 21838 Gene mRNA histone acetylation NA NA qRT-PCR; ChIp assay etc. no "Thy-1 expression in lung fibroblasts decreased with increased time after LPS challenge and diminished at 72 hrs. The acetylation of histone H4 (Ace-H4) decreased in the Thy-1 promoter region in response to LPS. In addition, all the above changes could be attenuated by depletion of TLR4 gene." 23305530 Epigenetic regulation of Thy-1 gene expression by histone modification is involved in lipopolysaccharide-induced lung fibroblast proliferation 2013 lung acute_lung_injury mus_musculus Timp1 21857 Gene mRNA up-regulation NA NA BAL; Immunohistochemistry; Neutrophil chemotaxis assay etc. yes "TIMP-1 contributes significantly to the regulation of acute lung injury, functioning to limit inflammation and lung permeability." 15947421 Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in bleomycin-exposed mice 2005 lung cystic_fibrosis homo_sapiens TLR2 7097 Gene mRNA promoter hypomethylation NA NA Dual-luciferase reporter assay; qRT-PCR; etc. no TLR2 expression is epigenetically up-regulated via promoter hypomethylation in CF bronchial epithelial cells and suggest that TLR2 overexpression or prolonged activation of TLR2 signaling might be critical in CF pathogenesis. 16478769 Promoter hypomethylation of Toll-like receptor-2 gene is associated with increased proinflammatoryresponse toward bacterial peptidoglycan in cystic fibrosis bronchial epithelial cells 2006 lung pulmonary_hypertension mus_musculus E2f3 13557 Gene mRNA up-regulation E2f3 NA EDU assay; Dual-luciferase reporter assay etc. no "Transcriptional induction of miR-210 in HPASMC is hypoxia-inducible factor-1a dependent. Inhibition of miR-210 in HPASMC caused a significant decrease in cell number due to increased apoptosis. MiR-210 mediates its antiapoptotic effects via the regulation of transcription factor E2F3, a direct target of miR-210." 22886504 MiR-210 has an antiapoptotic effect in pulmonary artery smooth muscle cells during hypoxia 2012 lung idiopathic_pulmonary_fibrosis homo_sapiens NOX4 50507 Gene mRNA dysregulation TGFBR2; NOX4 NA Dual-luciferase reporter assay; ISH etc. no "Transforming growth factor-B1 (TGF-B1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). MiR-9-5p has an inhibitory effect on TGF-B receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-B1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. TGF-B1 induces miR-9-5p expression as a self-limiting homeostatic response." 26315535 MiR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Nox4 50490 Gene mRNA dysregulation Tgfbr2; Nox4 NA Dual-luciferase reporter assay; ISH etc. no "Transforming growth factor-B1 (TGF-B1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). MiR-9-5p has an inhibitory effect on TGF-B receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-B1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. TGF-B1 induces miR-9-5p expression as a self-limiting homeostatic response." 26315535 MiR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2 2015 lung idiopathic_pulmonary_fibrosis mus_musculus Tgfbr2 21813 Gene mRNA dysregulation Tgfbr2; Nox4 NA Dual-luciferase reporter assay; ISH etc. no "Transforming growth factor-B1 (TGF-B1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). MiR-9-5p has an inhibitory effect on TGF-B receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-B1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. TGF-B1 induces miR-9-5p expression as a self-limiting homeostatic response." 26315535 MiR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2 2015 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFBR2 7048 Gene mRNA dysregulation TGFBR2; NOX4 NA Dual-luciferase reporter assay; ISH etc. no "Transforming growth factor-B1 (TGF-B1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). MiR-9-5p has an inhibitory effect on TGF-B receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-B1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p prevents its anti-fibrotic effect both in vitro and in vivo. In lung specimens from patients with IPF, high levels of miR-9-5p are found. TGF-B1 induces miR-9-5p expression as a self-limiting homeostatic response." 26315535 MiR-9-5p suppresses pro-fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2 2015 lung pulmonary_fibrosis rattus_norvegicus Thy1 24832 Gene mRNA histone acetylation NA NA qRT-PCR; Chromatin immunoprecipitation assay; Immunofluorescence etc. no "Treatment with the histone deacetylase inhibitor trichostatin A (TSA) restored Thy-1 expression in Thy-1(-) cells in a time-dependent and concentration-dependent fashion and was associated with enrichment of histone acetylation. TSA treatment cancause Thy-1 depletion of trimethylated H3K27, concurrent with enrichment of trimethylated H3K4 and acetylated H4. Previously hypermethylated CpG sitesin the Thy-1 promoter region was demethylated by TSA. Thy-1 silencing is regulated by histone modifications in addition to promoter hypermethylation in lung fibroblasts. Additionally, alteration of histone modifications alters DNA methylation." 20724553 Epigenetic regulation of thy-1 by histone deacetylase inhibitor in rat lung fibroblasts 2011 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Hdac2 84577 Gene mRNA histone acetylation NA NA qRT-PCR; Masson's trichrome staining etc. no TSA attenuates pulmonary fibrosis and it can inhibit HDAC2 expression at the gene and protein level. 25363222 Prevention of Pulmonary Fibrosis via Trichostatin A (TSA) in Bleomycin Induced Rats 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Twist1 22160 Gene mRNA up-regulation NA P53 signaling pathway; RUNX2 signaling pathway; P65 signaling pathway qRT-PCR; Dual-luciferase reporter assay; Immunoblot etc. no Twist1 promotes survival and accumulation of fibroblasts by shaping their responsiveness to growth factor stimulation. 19893041 "Gene expression profiling of pulmonary fibrosis identifies Twist1 as an antiapoptotic molecular ""rectifier"" of growth factor signaling" 2009 lung idiopathic_pulmonary_fibrosis mus_musculus Lin28b 380669 Gene mRNA dysregulation Lin28b NA Masson's trichrome staining; Immunohistochemistry; qRT-PCR etc. no Upregulation of Lin28B contributes to idiopathic pulmonary fibrosis. Lin28B causes epithelial-mesenchymal transition (EMT) by inhibition of let-7d. Lin28B is one of the targets of microRNA-26a. MiR-26a enhances the expression of let-7d via targeting regulation of Lin28B. A regulatory network among miRNAs involved in the progression of IPF. 26787543 MiR-26a suppresses EMT by disrupting the Lin28B/let-7d axis: potential cross-talks among miRNAs in IPF 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens LIN28B 389421 Gene mRNA dysregulation LIN28B NA Masson's trichrome staining; Immunohistochemistry; qRT-PCR etc. no Upregulation of Lin28B contributes to idiopathic pulmonary fibrosis. Lin28B causes epithelial-mesenchymal transition (EMT) by inhibition of let-7d. Lin28B is one of the targets of microRNA-26a. MiR-26a enhances the expression of let-7d via targeting regulation of Lin28B. A regulatory network among miRNAs involved in the progression of IPF. 26787543 MiR-26a suppresses EMT by disrupting the Lin28B/let-7d axis: potential cross-talks among miRNAs in IPF 2016 lung idiopathic_pulmonary_fibrosis homo_sapiens FOXO3 2309 Gene mRNA up-regulation FOXO3A NA qRT-PCR; In Situ Hybridization For miR-96 etc. no "When IPF fibroblasts interact with collagen-rich matrix, pathologically increased miR-96 expression inhibits FoxO3a function, causing IPF fibroblasts to maintain their pathological phenotype, which may contribute to the progression of IPF." 25172912 MicroRNA-96 inhibits FoxO3a function in IPF fibroblasts on type I collagen matrix 2014 lung idiopathic_pulmonary_fibrosis mus_musculus Ccn4 22402 Gene mRNA up-regulation NA NA qRT-PCR; Immunohistochemistry; etc. yes "WISP1 enhanced fibrogenesis by inducing EMT of ATII cells and increasing collagen production by fibroblasts, indicating that WISP1 exerts its profibrotic effects by a multitude of autocrine and paracrine effects in the lung." 19287097 WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens CCN4 8840 Gene mRNA up-regulation NA NA qRT-PCR; Immunohistochemistry; etc. no "WISP1 enhanced fibrogenesis by inducing EMT of ATII cells and increasing collagen production by fibroblasts, indicating that WISP1 exerts its profibrotic effects by a multitude of autocrine and paracrine effects in the lung." 19287097 WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis 2009 lung idiopathic_pulmonary_fibrosis homo_sapiens FZD2 2535 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "Wnt1, 7b and 10b, Fzd2 and 3, beta-catenin, and Lef4 expression was significantly increased in IPF." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens FZD3 7976 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "Wnt1, 7b and 10b, Fzd2 and 3, beta-catenin, and Lef4 expression was significantly increased in IPF." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens CTNNB1 1499 Gene mRNA up-regulation NA WNT/B-CATENIN signaling pathway Immunohistochemistry; qRT-PCR etc. no "Wnt1, 7b and 10b, Fzd2 and 3, beta-catenin, and Lef4 expression was significantly increased in IPF." 18478089 Functional Wnt signaling is increased in idiopathic pulmonary fibrosis 2008 lung idiopathic_pulmonary_fibrosis homo_sapiens ARHGEF3 50650 Gene mRNA histone acetylation NA NA qRT-PCR; Immunohistochemistry etc. no "XPLN depletion stimulated SPARC expression and Akt phosphorylation on Ser473. TGF-B1 treatment down-regulated XPLN via Smad 2/3. XPLN mRNA expression was up-regulated upon treatment with HDAC inhibitors in a concentration-dependent manner, and TGF-B1-induced SPARC expression was reversed by entinostat treatment. MTORC1 inhibition by rapamycin and Raptor depletion stimulated SPARC expression." 28315487 XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts 2017 lung idiopathic_pulmonary_fibrosis homo_sapiens SPARC 6678 Gene mRNA histone acetylation NA NA qRT-PCR; Immunohistochemistry etc. no "XPLN depletion stimulated SPARC expression and Akt phosphorylation on Ser473. TGF-B1 treatment down-regulated XPLN via Smad 2/3. XPLN mRNA expression was up-regulated upon treatment with HDAC inhibitors in a concentration-dependent manner, and TGF-B1-induced SPARC expression was reversed by entinostat treatment. MTORC1 inhibition by rapamycin and Raptor depletion stimulated SPARC expression." 28315487 XPLN is modulated by HDAC inhibitors and negatively regulates SPARC expression by targeting mTORC2 in human lung fibroblasts 2017 pancreas cystic_fibrosis mus_musculus Spink1 20730 Gene mRNA up-regulation NA NA pancreatic expression array; H&E staining etc. no "Because spink3 may be an important serine protease inhibitor, its up-regulation may reflect an important endogenous cytoprotective mechanism in preventing further injury. The up-regulation of spink3 was specific; The mouse homologue of the zymogen-processing protein zg-16p was also highly expressed in the pancreas but sharply down-regulated early in the course of injury." 15097871 Differential expression of the trypsin inhibitor SPINK3 mRNA and the mouse ortholog of secretory granule protein ZG-16p mRNA in the mouse pancreas after repetitive injury 2004 pancreas pancreatitis_chronic mus_musculus Zg16 171449 Gene mRNA down-regulation NA NA pancreatic expression array; H&E staining etc. no "Because spink3 may be an important serine protease inhibitor, its up-regulation may reflect an important endogenous cytoprotective mechanism in preventing further injury. The up-regulation of spink3 was specific; The mouse homologue of the zymogen-processing protein zg-16p was also highly expressed in the pancreas but sharply down-regulated early in the course of injury." 15097871 Differential expression of the trypsin inhibitor SPINK3 mRNA and the mouse ortholog of secretory granule protein ZG-16p mRNA in the mouse pancreas after repetitive injury 2004 pancreas pancreatitis homo_sapiens NFKB1 4790 Gene mRNA up-regulation SURVIVIN; CIAP1 NA qRT-PCR; rela transcription factor assay no "Islets in cp not only evade immune attack by nonexposure of functional death receptors in the presence of trail-r4 but also additionally neoexpress nfkappab and its target genes, survivin and ciap1, to protect themselves from apoptosis." 16127431 Parenchymal regression in chronic pancreatitis spares islets reprogrammed for the expression of NFkappaB and IAPs 2005 pancreas pancreatitis homo_sapiens BIRC3 330 Gene mRNA up-regulation SURVIVIN; CIAP1 NA qRT-PCR; rela transcription factor assay no "Islets in cp not only evade immune attack by nonexposure of functional death receptors in the presence of trail-r4 but also additionally neoexpress nfkappab and its target genes, survivin and ciap1, to protect themselves from apoptosis." 16127431 Parenchymal regression in chronic pancreatitis spares islets reprogrammed for the expression of NFkappaB and IAPs 2005 pancreas cystic_fibrosis rattus_norvegicus Bax 24887 Gene mRNA down-regulation NA NA RT-PCR etc. yes "Losartan prevents apoptosis of pancreatic acinar cell by blocking at1r during the development of pancreatic fibrosis. This action may be associated with its regulation of apoptosis-associated genes, such as bax, bak, and bcl-2 mrna. The results of present study suggest that angiotensin ii probably mediates pancreatic acinar cell apoptosis during the course of pancreatic fibrosis." 15502641 Angiotensin II mediates acinar cell apoptosis during the development of rat pancreatic fibrosis by AT1R 2004 pancreas cystic_fibrosis rattus_norvegicus Bcl2 24224 Gene mRNA down-regulation NA NA RT-PCR etc. yes "Losartan prevents apoptosis of pancreatic acinar cell by blocking at1r during the development of pancreatic fibrosis. This action may be associated with its regulation of apoptosis-associated genes, such as bax, bak, and bcl-2 mrna. The results of present study suggest that angiotensin ii probably mediates pancreatic acinar cell apoptosis during the course of pancreatic fibrosis." 15502641 Angiotensin II mediates acinar cell apoptosis during the development of rat pancreatic fibrosis by AT1R 2004 pancreas pancreatitis_chronic mus_musculus Col4a1 12826 Gene mRNA dysregulation NA NA RT-PCR; cell prolimmunofluorescenceeration assay etc. yes "The effect of troglitazone on alpha1(i) procollagen mrna and mcp-1 mrna was unaffected by inhibition of endogenous ppargamma1 receptor activity. These results suggest that troglitazone may serve as novel therapeutic agent for the treatment of chronic pancreatitis. The antifibrotic effect of troglitazone appears to be mediated, in part, via a ppargamma-independent mechanism." 15211114 Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPARgamma-independent mechanism 2004 pancreas pancreatitis_chronic mus_musculus MCP-1 100009115 Gene mRNA dysregulation NA NA RT-PCR; cell prolimmunofluorescenceeration assay etc. yes "The effect of troglitazone on alpha1(i) procollagen mrna and mcp-1 mrna was unaffected by inhibition of endogenous ppargamma1 receptor activity. These results suggest that troglitazone may serve as novel therapeutic agent for the treatment of chronic pancreatitis. The antifibrotic effect of troglitazone appears to be mediated, in part, via a ppargamma-independent mechanism." 15211114 Troglitazone inhibits the progression of chronic pancreatitis and the profibrogenic activity of pancreatic stellate cells via a PPARgamma-independent mechanism 2004 pancreas pancreatitis homo_sapiens NOTCH-2 4853 Gene mRNA dysregulation NA NOTCH SIGNALING PATHWAY qRT-PCR; immunohistochemistry no "These findings suggest a possible role of the notch pathway during pancreatic regeneration since jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease." 17114010 Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway 2006 pancreas pancreatitis homo_sapiens NOTCH-3 4854 Gene mRNA dysregulation NA NOTCH SIGNALING PATHWAY qRT-PCR; immunohistochemistry no "These findings suggest a possible role of the notch pathway during pancreatic regeneration since jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease." 17114010 Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway 2006 pancreas pancreatitis homo_sapiens NOTCH-4 4855 Gene mRNA dysregulation NA NOTCH SIGNALING PATHWAY qRT-PCR; immunohistochemistry no "These findings suggest a possible role of the notch pathway during pancreatic regeneration since jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease." 17114010 Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway 2006 pancreas cystic_fibrosis homo_sapiens CFTR 1080 Gene mRNA dysregulation NA NA NA no "We conclude that severe reduction in cftr mrna causes cf, but can have different consequences in the lung and pancreas." 1721624 Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis 1991 pancreas cystic_fibrosis homo_sapiens W1316X NA NA mRNA dysregulation NA NA NA no "We conclude that severe reduction in cftr mrna causes cf, but can have different consequences in the lung and pancreas." 1721624 Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis 1991 skin scleroderma_systemic homo_sapiens CCR7 1236 Gene mRNA dysregulation NA NA RT-PCR no "We could confirm data of previous studies indicating that gene expression of il-6 is up-regulated in ls lesions as compared to healthy skin. Moreover, we have shown for the first time a significant increase of mrna levels of ccr7 and ccl5;Rantes in ls lesions indicating an important pathogenetic role of chemokines in ls." 21616095 Significantly increased CCL5/RANTES and CCR7 mRNA levels in localized scleroderma 2011 kidney kidney_diseases mus_musculus Plekho1 67220 Gene mRNA down-regulation CX43 NRF2 SIGNALING PATHWAY immunofluorescence no "CKIP-1 acts downstream to CX43 on the activation of NRF2 signaling pathway to protect from renal fibrosis in diabetes, the mechanism of which might be related to the interaction of CKIP-1 with NRF2 through Cx43 carboxyl terminus (CT)." 33276097 CKIP-1 acts downstream to Cx43 on the activation of Nrf2 signaling pathway to protect from renal fibrosis in diabetes 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LGALS3 3958 Gene mRNA up-regulation NA NA Fluorescence intensity yes "Galectin (Gal)-3 is a central regulator of fibrosis in the lung with expression upregulated in bronchoalveolar lavage (BAL) fluid and serum of IPF patients, and further elevation observed during exacerbations. The profibrotic function of Gal-3 is multifactorial due to its ability to cross-link and promote signalling via multiple cell surface receptors including integrins and growth factor receptors, such as transforming growth factor-beta, vascular endothelial growth factor and platelet-derived growth factor (PDGF) receptors. Constitutive global deficiency of Gal-3 leads to attenuated fibrosis in murine models." 33214209 Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens NES 10763 Gene mRNA up-regulation TbetaRI TGF-BETA SIGNALING PATHWAY qRT-PCR; Immunohistochemistry; Immunofluorescence etc. no "Nestin regulates the vesicular trafficking system by promoting recycling of TbetaRI to the cell membrane through Rab11 and thereby contributes to the progression of pulmonary fibrosis. More importantly, precise targeting of Nestin expression within lung myofibroblasts can alleviate lung fibrogenesis and may represent a potential therapeutic strategy for IPF." 34625478 Nestin promotes pulmonary fibrosis?via?facilitating recycling of TGF-beta receptor I 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Nes 18008 Gene mRNA up-regulation TbetaRI TGF-BETA SIGNALING PATHWAY qRT-PCR; Immunohistochemistry; Immunofluorescence etc. no "Nestin regulates the vesicular trafficking system by promoting recycling of TbetaRI to the cell membrane through Rab11 and thereby contributes to the progression of pulmonary fibrosis. More importantly, precise targeting of Nestin expression within lung myofibroblasts can alleviate lung fibrogenesis and may represent a potential therapeutic strategy for IPF." 34625478 Nestin promotes pulmonary fibrosis?via?facilitating recycling of TGF-beta receptor I 2021 lung pulmonary_fibrosis mus_musculus Arg1 11846 Gene mRNA up-regulation NA ARGINASE-ORNITHINE PATHWAY qRT-PCR; Western Blot etc. yes "Arginase 1 (Arg1) is a key enzyme in the cycle and can metabolize arginine as ornithine. WB results showed that the content of Arg1 in the lung tissue of mice induced by BLM was significantly increased, and TL can significantly inhibit the expression of arginase 1(Arg1), argininosuccinate synthase (ASS1), carbamoyl phosphate synthase (CPS1) and ornithine carbamoyl transferase (OTC)." 33995084 Tianlongkechuanling Inhibits Pulmonary Fibrosis Through Down-Regulation of Arginase-Ornithine Pathway 2021 lung pulmonary_fibrosis mus_musculus Cort 12854 Gene mRNA down-regulation NA NA RT-PCR; Immunofluorescence; Western Blot etc. no "Interestingly, activation of pulmonary fibroblasts with TGF-beta1 almost completelyinhibited cortistatin gene expression and bleomycin challenge moderately reduced its expression in lungs." 34237151 Protective role of cortistatin in pulmonary inflammation and fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens IGF1 3479 Gene mRNA up-regulation NA IGF1 SIGNALING PATHWAY ELISA; Immunofluorescence; RT-PCR etc. no "Western blotting showed that the levels of IGF1, IGFR-1, PI3K, AKT and p-AKT in lung tissues of patients with IPF were significantly higher than those in normal lung tissues. This indicated that the IGF1 signaling pathway is activated in IPF conditions." 34329195 Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CDKN1A 1026 Gene mRNA up-regulation NA NA ELISA; Immunofluorescence; RT-PCR etc. no Immunofluorescence showed that there were significantly increased expression of senescence key protein (P21) in AECs and the increased p21 were accompanied by up-regulated CF (as indicated by FUT8 and LCA levels). 34329195 Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CDKN2A 1029 Gene mRNA up-regulation NA NA ELISA; immunofluorescence; RT-PCR etc. no "Western blotting also showed that the levels of senescence key protein (P21, P16) and FUT8 were upregulated in IPF lung tissue." 34329195 Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens FUT8 2530 Gene mRNA up-regulation NA NA ELISA; immunofluorescence; RT-PCR etc. no "Western blotting also showed that the levels of senescence key protein (P21, P16) and FUT8 were upregulated in IPF lung tissue." 34329195 Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CFL1 1072 Gene mRNA up-regulation NA NA qRT-PCR; Western Blot etc. no "Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05)." 34090209 Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SIRT2 22933 Gene mRNA up-regulation Smad2; Smad3 Smad2/3 pathway RT-PCR; Western Blot; Immunofluorescence etc. no Sirt2 expression was upregulated in transforming growth factor-beta1 (TGF-beta1) treated human embryonic lung fibroblasts. 34925016 Inhibition of Sirt2 Alleviates Fibroblasts Activation and Pulmonary Fibrosis?via?Smad2/3 Pathway 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Mettl3 56335 Gene mRNA up-regulation NA NA Dot-Blot; Western Blot; Immunofluorescence etc. no "In this study, we reveal that m6A modification is upregulated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model, FMT-derived myofibroblasts, and IPF patient lung samples. Lowering m6A levels through silencing methyltransferase-like 3 (METTL3) inhibits the FMT process in vitro and in vivo." 34111558 m6A modification regulates lung fibroblast-to-myofibroblast transition through modulating KCNH6 mRNA translation 2021 lung pulmonary_fibrosis mus_musculus Foxk2 68837 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Dual-lucimmunofluorescenceerase Reporter Assay etc. no "Next, we detected circHIPK3 and miR-30a-3p expression levels in this model and observed circHIPK3 was up-regulated, while miR-30a-3p was markedly down-regulated in a time-dependent manner. Besides, the lactate levels and the protein expression of Foxk2 and glycolytic enzymes (HK2, PFKM, PKM2, and PDK1) were also upregulated after silica exposure." 34239356 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner 2021 lung pulmonary_fibrosis mus_musculus Hk2 15277 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Dual-lucimmunofluorescenceerase Reporter Assay etc. no "Next, we detected circHIPK3 and miR-30a-3p expression levels in this model and observed circHIPK3 was up-regulated, while miR-30a-3p was markedly down-regulated in a time-dependent manner. Besides, the lactate levels and the protein expression of Foxk2 and glycolytic enzymes (HK2, PFKM, PKM2, and PDK1) were also upregulated after silica exposure." 34239356 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner 2021 lung pulmonary_fibrosis mus_musculus Pfkm 18642 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Dual-lucimmunofluorescenceerase Reporter Assay etc. no "Next, we detected circHIPK3 and miR-30a-3p expression levels in this model and observed circHIPK3 was up-regulated, while miR-30a-3p was markedly down-regulated in a time-dependent manner. Besides, the lactate levels and the protein expression of Foxk2 and glycolytic enzymes (HK2, PFKM, PKM2, and PDK1) were also upregulated after silica exposure." 34239356 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner 2021 lung pulmonary_fibrosis mus_musculus Pkm 18746 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Dual-lucimmunofluorescenceerase Reporter Assay etc. no "Next, we detected circHIPK3 and miR-30a-3p expression levels in this model and observed circHIPK3 was up-regulated, while miR-30a-3p was markedly down-regulated in a time-dependent manner. Besides, the lactate levels and the protein expression of Foxk2 and glycolytic enzymes (HK2, PFKM, PKM2, and PDK1) were also upregulated after silica exposure." 34239356 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner 2021 lung pulmonary_fibrosis mus_musculus Pdk1 228026 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Dual-lucimmunofluorescenceerase Reporter Assay etc. no "Next, we detected circHIPK3 and miR-30a-3p expression levels in this model and observed circHIPK3 was up-regulated, while miR-30a-3p was markedly down-regulated in a time-dependent manner. Besides, the lactate levels and the protein expression of Foxk2 and glycolytic enzymes (HK2, PFKM, PKM2, and PDK1) were also upregulated after silica exposure." 34239356 CircHIPK3 regulates pulmonary fibrosis by facilitating glycolysis in miR-30a-3p/FOXK2-dependent manner 2021 lung pulmonary_fibrosis mus_musculus Aldh2 11669 Gene mRNA dysregulation NA NA NA no "Two genes from these analyses that were decreased in expression at Day 14 and reversed at Day 30, Aldh2 and Nr3c1, were selected for further analysis. Enhancement of endogenous expression of either gene by CRISPR activation in cultured human idiopathic pulmonary fibrosis fibroblasts was sufficient to reduce profibrotic gene expression, fibronectin deposition, and collagen gel compaction, consistent with roles for these genes in fibroblast deactivation." 33493091 Spontaneous Lung Fibrosis Resolution Reveals Novel Antifibrotic Regulators 2021 lung pulmonary_fibrosis mus_musculus Nr3c1 14815 Gene mRNA dysregulation NA NA NA no "Two genes from these analyses that were decreased in expression at Day 14 and reversed at Day 30, Aldh2 and Nr3c1, were selected for further analysis. Enhancement of endogenous expression of either gene by CRISPR activation in cultured human idiopathic pulmonary fibrosis fibroblasts was sufficient to reduce profibrotic gene expression, fibronectin deposition, and collagen gel compaction, consistent with roles for these genes in fibroblast deactivation." 33493091 Spontaneous Lung Fibrosis Resolution Reveals Novel Antifibrotic Regulators 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MDM4 4194 Gene mRNA up-regulation TP53 Mdm4-p53 pathway qRT-PCR; ELISA; Flow Cytometry etc. no "In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice." 33688918 Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Mdm4 17248 Gene mRNA up-regulation Trp53 Mdm4-p53 pathway qRT-PCR; ELISA; Flow Cytometry etc. no "In this study, we found that mouse double minute 4 homolog (MDM4) is highly expressed in the fibrotic lesions of human IPF and experimental pulmonary fibrosis in aged mice." 33688918 Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SIRT3 23410 Gene mRNA down-regulation NA NA PCR; Western Blot etc. no "We showed that sirtuin 3 (SIRT3), a mitochondrial protein regulating cell fate and aging, is deficient in the AECs of idiopathic pulmonary fibrosis (IPF) patients and that asbestos- and bleomycin-induced lung fibrosis is augmented in Sirt3 knockout (Sirt3-/-) mice associated with AEC mtDNA damage and intrinsic apoptosis." 34202229 "SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment" 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Sirt3 64384 Gene mRNA down-regulation NA NA PCR; Western Blot etc. no "We showed that sirtuin 3 (SIRT3), a mitochondrial protein regulating cell fate and aging, is deficient in the AECs of idiopathic pulmonary fibrosis (IPF) patients and that asbestos- and bleomycin-induced lung fibrosis is augmented in Sirt3 knockout (Sirt3-/-) mice associated with AEC mtDNA damage and intrinsic apoptosis." 34202229 "SIRT3 Overexpression Ameliorates Asbestos-Induced Pulmonary Fibrosis, mt-DNA Damage, and Lung Fibrogenic Monocyte Recruitment" 2021 lung pulmonary_fibrosis rattus_norvegicus Cdh1 83502 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Lats1 308265 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Fzd2 64512 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Gli1 140589 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Ctnna1 307505 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Sav1 299116 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Wnt11 140584 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Wnt7a 114850 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Bmp4 25296 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Wnt3a 303181 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Sox2 499593 Gene mRNA down-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Tp73 362675 Gene mRNA down-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Hippo signaling pathways genes included in this study were Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Wnt3a, Bmp4, Sox2, and Tp73. The fold change of Hippo signaling pathways genes identified that Cdh1, Lats1, Fzd2, Gli1, Ctnna1, Sav1, Wnt11, Wnt7a, Bmp4, and Wnt3a were highly expressed in BLM compared with normal control samples. Sox2 and Tp73 exhibited lower expression in BLM than in normal control groups." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis rattus_norvegicus Yap1 363014 Gene mRNA up-regulation NA Hippo signaling pathways ELISA; qRT-PCR; Western Blot etc. yes "Moreover, it is worth noticing that the expression of YAP dramatically increased with BLM induction and then suppressed by ICA treatment." 34536758 Icariin attenuates bleomycin-induced pulmonary fibrosis by targeting Hippo/YAP pathway 2021 lung pulmonary_fibrosis mus_musculus Map1lc3b 67443 Gene mRNA up-regulation NA NA ELISA; Immunofluorescence; Western Blot etc. yes "In these genes we find Map1lc3, Cxcl2, and TNF genes up-regulation, which means autophagy regulation was activated and inflammatory response in macrophages." 33720480 Silica dust exposure induces pulmonary fibrosis through autophagy signaling 2021 lung pulmonary_fibrosis mus_musculus Cxcl2 20310 Gene mRNA up-regulation NA NA ELISA; Immunofluorescence; Western Blot etc. yes "In these genes we find Map1lc3, Cxcl2, and TNF genes up-regulation, which means autophagy regulation was activated and inflammatory response in macrophages." 33720480 Silica dust exposure induces pulmonary fibrosis through autophagy signaling 2021 lung pulmonary_fibrosis mus_musculus Tnf 21926 Gene mRNA up-regulation NA NA ELISA; Immunofluorescence; Western Blot etc. yes "In these genes we find Map1lc3, Cxcl2, and TNF genes up-regulation, which means autophagy regulation was activated and inflammatory response in macrophages." 33720480 Silica dust exposure induces pulmonary fibrosis through autophagy signaling 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens IL22 50616 Gene mRNA down-regulation NA TGF-BETA SIGNALING PATHWAY qRT-PCR; Enzyme-linked Immunosorbent Assay; Western Blot etc. no The expression of IL-22 was lower in the peripheral blood of IPF patients and correlated negatively with the disease severity. 34459137 Protective function of interleukin-22 in pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MYRF 745 Gene mRNA down-regulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens CLDN18 51208 Gene mRNA down-regulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens COL6A3 1293 Gene mRNA dysregulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens PRSS8 5652 Gene mRNA dysregulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens RRAS 6237 Gene mRNA dysregulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens SBNO1 55206 Gene mRNA dysregulation NA NA co-expression gene pair analysis; functional enrichment analysis etc. no "A total of 343 DEGs and 21 DEMs were identified between IPF and normal samples. CLDN18, COL6A3, MYRF, PRSS8, RRAS, and SBNO1 were identified as potential IPF biomarkers. In addition, 17 miRNA-target relationship pairs were obtained. The up-regulation of hsa-miR-657, hsa-miR-671-5p, hsa-miR-198, and hsa-miR-940 could regulate the down-regulation of MYRF and the up-regulation of hsa-miR-198 and hsa-miR-373-3p could regulate the down-regulation of RRAS and CLDN18, respectively. Our data indicated that PRSS8, hsa-miR-614, and hsa-miR-503-5p might be involved in the migration and invasion of IPF related cells." 34666057 Screening of Biomarkers Involved in Idiopathic Pulmonary Fibrosis and Regulation of Upstream miRNAs 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP1 4312 Gene mRNA up-regulation NA MAPK PATHWAY GO and pathway enrichment analysis etc. no "MMP1, SPP1, and BPIFB1 were the top three DEGs with the highest significant up-regulation. These DEGs played an important role in the occurrence of IPF through the MAPK (mitogen-activated protein kinase) signaling pathway." 34734011 Bioinformatic analysis of differentially expressed genes and pathways in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SPP1 6696 Gene mRNA up-regulation NA MAPK PATHWAY GO and pathway enrichment analysis etc. no "MMP1, SPP1, and BPIFB1 were the top three DEGs with the highest significant up-regulation. These DEGs played an important role in the occurrence of IPF through the MAPK (mitogen-activated protein kinase) signaling pathway." 34734011 Bioinformatic analysis of differentially expressed genes and pathways in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens BPIFB1 92747 Gene mRNA up-regulation NA MAPK PATHWAY GO and pathway enrichment analysis etc. no "MMP1, SPP1, and BPIFB1 were the top three DEGs with the highest significant up-regulation. These DEGs played an important role in the occurrence of IPF through the MAPK (mitogen-activated protein kinase) signaling pathway." 34734011 Bioinformatic analysis of differentially expressed genes and pathways in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens GABARAPL1 23710 Gene mRNA down-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "By combining the PPI network, miRNA-target network, and functional enrichment analysis, we identified potential biomarkers including GABARAPL1, SGTA, ARRB1, GPX8, and VCAM1 for IPF. Among them, GABARAPL1, SGTA, and ARRB1 exhibited lower expression levels in IPF while GPX8 and VCAM1 were both downregulated in IPF." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens GPX8 493869 Gene mRNA up-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "In the network, there were 227 nodes, including 122 upregulated and 105 downregulated genes. Nodes with degree >= 7 were considered hub genes, including GABARAPL1, GPX8, SGTA, VCAM1, ARRB1, SPP1, and HLA-B." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SGTA 6449 Gene mRNA down-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "By combining the PPI network, miRNA-target network, and functional enrichment analysis, we identified potential biomarkers including GABARAPL1, SGTA, ARRB1, GPX8, and VCAM1 for IPF. Among them, GABARAPL1, SGTA, and ARRB1 exhibited lower expression levels in IPF while GPX8 and VCAM1 were both downregulated in IPF." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens VCAM1 7412 Gene mRNA up-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "In the network, there were 227 nodes, including 122 upregulated and 105 downregulated genes. Nodes with degree >= 7 were considered hub genes, including GABARAPL1, GPX8, SGTA, VCAM1, ARRB1, SPP1, and HLA-B." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens ARRB1 408 Gene mRNA down-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "By combining the PPI network, miRNA-target network, and functional enrichment analysis, we identified potential biomarkers including GABARAPL1, SGTA, ARRB1, GPX8, and VCAM1 for IPF. Among them, GABARAPL1, SGTA, and ARRB1 exhibited lower expression levels in IPF while GPX8 and VCAM1 were both downregulated in IPF." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SPP1 6696 Gene mRNA up-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "In the network, there were 227 nodes, including 122 upregulated and 105 downregulated genes. Nodes with degree >= 7 were considered hub genes, including GABARAPL1, GPX8, SGTA, VCAM1, ARRB1, SPP1, and HLA-B." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens HLA-B 3106 Gene mRNA down-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no "In the network, there were 227 nodes, including 122 upregulated and 105 downregulated genes. Nodes with degree >= 7 were considered hub genes, including GABARAPL1, GPX8, SGTA, VCAM1, ARRB1, SPP1, and HLA-B." 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LDLR 3949 Gene mRNA up-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no We found that LDLR and RAB11FIP1 were regulated by most miRNAs. Both were upregulated in IPF_S compared to N_CTL. 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens RAB11FIP1 80223 Gene mRNA up-regulation NA NA Differentially Expressed Analysis; Western Blot etc. no We found that LDLR and RAB11FIP1 were regulated by most miRNAs. Both were upregulated in IPF_S compared to N_CTL. 34285914 Identification and Validation of Potential Biomarkers and Pathways for Idiopathic Pulmonary Fibrosis by Comprehensive Bioinformatics Analysis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP7 4316 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Some genes that were up-regulated in fibrosis samples, such as MMP7, TNF, and PLAU, were genes involved in the tissue repair process." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TNF 7124 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Some genes that were up-regulated in fibrosis samples, such as MMP7, TNF, and PLAU, were genes involved in the tissue repair process." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens PLAU 5328 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Some genes that were up-regulated in fibrosis samples, such as MMP7, TNF, and PLAU, were genes involved in the tissue repair process." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFBI 7045 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "TGFBI, a gene that is known to participate in the EMT process, is up-regulated in fibrosis." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP11 4320 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Genes involved in coagulation, such as MMP7 and MMP11, as well as genes involved in EMT, such as COL3A1, COL1A1, and ADAM12 were also up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens COL3A1 1281 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Genes involved in coagulation, such as MMP7 and MMP11, as well as genes involved in EMT, such as COL3A1, COL1A1, and ADAM12 were also up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens COL1A1 1277 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Genes involved in coagulation, such as MMP7 and MMP11, as well as genes involved in EMT, such as COL3A1, COL1A1, and ADAM12 were also up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens ADAM12 8038 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Genes involved in coagulation, such as MMP7 and MMP11, as well as genes involved in EMT, such as COL3A1, COL1A1, and ADAM12 were also up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CD28 940 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "CD28 and CD86 were up-regulated, and CD274 (encoding the co-inhibitory receptor PD-L1) were down-regulated in both minimal and established fibrosis." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CD86 942 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "CD28 and CD86 were up-regulated, and CD274 (encoding the co-inhibitory receptor PD-L1) were down-regulated in both minimal and established fibrosis." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CD274 29126 Gene mRNA down-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "CD28 and CD86 were up-regulated, and CD274 (encoding the co-inhibitory receptor PD-L1) were down-regulated in both minimal and established fibrosis." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR4 7099 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "In our IPF samples, TLRs that could recognize both bacteria (TLR4 and TLR6) and viruses (TLR7 and TLR8) were significantly up-regulated. Of the remainder of the TLRs, only TLR2 was down-regulated, and almost all other TLRs were up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR6 10333 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "In our IPF samples, TLRs that could recognize both bacteria (TLR4 and TLR6) and viruses (TLR7 and TLR8) were significantly up-regulated. Of the remainder of the TLRs, only TLR2 was down-regulated, and almost all other TLRs were up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR7 51284 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "In our IPF samples, TLRs that could recognize both bacteria (TLR4 and TLR6) and viruses (TLR7 and TLR8) were significantly up-regulated. Of the remainder of the TLRs, only TLR2 was down-regulated, and almost all other TLRs were up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR8 51311 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "In our IPF samples, TLRs that could recognize both bacteria (TLR4 and TLR6) and viruses (TLR7 and TLR8) were significantly up-regulated. Of the remainder of the TLRs, only TLR2 was down-regulated, and almost all other TLRs were up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TLR2 7097 Gene mRNA down-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "In our IPF samples, TLRs that could recognize both bacteria (TLR4 and TLR6) and viruses (TLR7 and TLR8) were significantly up-regulated. Of the remainder of the TLRs, only TLR2 was down-regulated, and almost all other TLRs were up-regulated." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens NFKB1 4790 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Their downstream targets, including components of the NFKB pathway, such as NFKB1, TRAF3, PKD1, and CYLD, were also up-regulated in the IPF samples." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TRAF3 7187 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Their downstream targets, including components of the NFKB pathway, such as NFKB1, TRAF3, PKD1, and CYLD, were also up-regulated in the IPF samples." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens PKD1 5310 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Their downstream targets, including components of the NFKB pathway, such as NFKB1, TRAF3, PKD1, and CYLD, were also up-regulated in the IPF samples." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CYLD 1540 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Their downstream targets, including components of the NFKB pathway, such as NFKB1, TRAF3, PKD1, and CYLD, were also up-regulated in the IPF samples." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFB1 7040 Gene mRNA up-regulation TGFBR1 NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Important transforming growth factors, namely TGFB1, TGFB2, and TGFB3 and their receptor TGFBR1, were all up-regulated starting from the minimal fibrosis ." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFB2 7042 Gene mRNA up-regulation TGFBR1 NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Important transforming growth factors, namely TGFB1, TGFB2, and TGFB3 and their receptor TGFBR1, were all up-regulated starting from the minimal fibrosis ." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFB3 7043 Gene mRNA up-regulation TGFBR1 NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Important transforming growth factors, namely TGFB1, TGFB2, and TGFB3 and their receptor TGFBR1, were all up-regulated starting from the minimal fibrosis ." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens TGFBR1 7046 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Important transforming growth factors, namely TGFB1, TGFB2, and TGFB3 and their receptor TGFBR1, were all up-regulated starting from the minimal fibrosis ." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CASP1 834 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Additionally, CASP1, NLRC4, which participate in the activation of a cytokine storm, were all up-regulated in minimal fibrosis, while another cytokine storm trigger, IL18, was up-regulated in both minimal and established fibrosis regions." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens NLRC4 58484 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Additionally, CASP1, NLRC4, which participate in the activation of a cytokine storm, were all up-regulated in minimal fibrosis, while another cytokine storm trigger, IL18, was up-regulated in both minimal and established fibrosis regions." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens IL18 3606 Gene mRNA up-regulation NA NA Histological Analyses; Pre-operative MDCT Analyses etc. no "Additionally, CASP1, NLRC4, which participate in the activation of a cytokine storm, were all up-regulated in minimal fibrosis, while another cytokine storm trigger, IL18, was up-regulated in both minimal and established fibrosis regions." 33862585 The transition from normal lung anatomy to minimal and established fibrosis in idiopathic pulmonary fibrosis (IPF) 2021 lung silicosis rattus_norvegicus Tnf 24835 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; Western Blot etc. no "The qRT-PCR results showed that compared with the control group rats, the mRNA levels of Tnfa, Il1b and Il6 in lung tissues of the silica group were significantly increased." 34076355 Mesenchymal stem cells ameliorate silica-induced pulmonary fibrosis by inhibition of inflammation and epithelial-mesenchymal transition 2021 lung silicosis rattus_norvegicus Il1b 24494 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; Western Blot etc. no "The qRT-PCR results showed that compared with the control group rats, the mRNA levels of Tnfa, Il1b and Il6 in lung tissues of the silica group were significantly increased." 34076355 Mesenchymal stem cells ameliorate silica-induced pulmonary fibrosis by inhibition of inflammation and epithelial-mesenchymal transition 2021 lung silicosis rattus_norvegicus Il6 24498 Gene mRNA up-regulation NA NA qRT-PCR; ELISA; Western Blot etc. no "The qRT-PCR results showed that compared with the control group rats, the mRNA levels of Tnfa, Il1b and Il6 in lung tissues of the silica group were significantly increased." 34076355 Mesenchymal stem cells ameliorate silica-induced pulmonary fibrosis by inhibition of inflammation and epithelial-mesenchymal transition 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Pcbp3 59093 Gene mRNA up-regulation Pfkfb3 NA qRT-PCR; Immunofluorescence; Western Blot etc. yes "We evaluated the expression of PCBP3 in lung tissues and found that the protein levels of PCBP3 were markedly increased after bleomycin instillation, while anlotinib treatment decreased PCBP3 expression." 34603058 Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Pfkfb3 170768 Gene mRNA up-regulation NA NA qRT-PCR; Immunofluorescence; Western Blot etc. yes "These findings suggest that PCBP3 protein upregulation is an early and sustained event during fibroblast activation and that the profibrogenic effects of PCBP3 are mediated by PFKFB3 expression. Taken together, these data suggest that PCBP3 posttranscriptionally increases PFKFB3 expression by promoting its translation during myofibroblast activation." 34603058 Anlotinib Inhibits PFKFB3-Driven Glycolysis in Myofibroblasts to Reverse Pulmonary Fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens IGF1 3479 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SPP1 6696 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens PROM1 8842 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SOX2 6657 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP1 4312 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens COL1A1 1277 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens MMP7 4316 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens POSTN 10631 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens COL3A1 1281 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens COMP 1311 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LCN2 3934 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens IL6 3569 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens VEGFA 7422 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CDH5 1003 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens WNT3A 89780 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens ICAM1 3383 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens EDN1 1906 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CSF3 1440 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CAV1 857 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens HBEGF 1839 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "The 20 hub genes comprised 11 upregulated (IGF1, SPP1, PROM1, SOX2, MMP1, COL1A1, MMP7, POSTN, COL3A1, COMP, LCN2) and nine downregulated (IL6, VEGFA, CDH5, WNT3A, ICAM1, EDN1, CSF3, CAV1, HBEGF) genes." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CXCL14 9547 Gene mRNA up-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens DAPK2 23604 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens EMP2 2013 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens GPM6A 2823 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens STXBP6 29091 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens LRRC32 2615 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens ADRB1 153 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SLC6A4 6532 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens CCDC85A 114800 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens FOXF1 2294 Gene mRNA down-regulation NA NA GO and KEGG enrichment analysis; GSVA; Hub gene analysis etc. no "We identified 13 miRNAs (miR-107, miR-125a-5p, miR-133b, miR-140-5p, miR-142-3p, miR-199a-3p, miR-199a-5p, miR-199b-5p, miR-28-5p, miR-324-5p, miR-34c-5p, miR-429, and miR-520b) and 13 mRNAs (WNT3A, CDH5, DAPK2, EMP2, GPM6A, STXBP6, VEGFA, LRRC32, ADRB1, SLC6A4, CCDC85A, FOXF1, and CXCL14). All miRNAs were upregulated except miR-520b. All genes for these mRNAs were downregulated except CXCL14." 34522168 Integrated analysis of the molecular mechanisms in idiopathic pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Smad3 25631 Gene mRNA up-regulation NA NA qRT-PCR; Western Blot etc. yes Smad3 and Smad4 proteins were overexpressed in BLM-induced pulmonary fibrosis rats compared with normal rats. 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Smad4 50554 Gene mRNA up-regulation NA NA qRT-PCR; Western Blot etc. yes Smad3 and Smad4 proteins were overexpressed in BLM-induced pulmonary fibrosis rats compared with normal rats. 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Smad7 81516 Gene mRNA down-regulation NA NA qRT-PCR; Western Blot etc. yes "In addition, BLM significantly reduced Smad7 protein expression compared with normal control rats, and NFE (400 and 200?mg/kg) significantly upregulated Smad7 expression." 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Ccn2 64032 Gene mRNA up-regulation NA NA qRT-PCR; Western Blot etc. yes "Western blotting analysis showed that CTGF protein levels were upregulated in BLM-induced pulmonary fibrosis rats, and NFE (400 and 200?mg/kg) treatment downregulated its expression levels." 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Mapk3 50689 Gene mRNA down-regulation NA NA qRT-PCR; Western Blot etc. yes "Similarly, the protein level of ERK1/2 was significantly downregulated, while that of p-ERK1/2 was significantly upregulated in BLM-induced pulmonary fibrosis rats. NFE (400 and 200 mg/kg) treatment significantly and dose-dependently normalized the phosphorylation of ERK1/2, upregulated ERK1/2 protein levels, and downregulated p-ERK1/2 protein levels." 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung idiopathic_pulmonary_fibrosis rattus_norvegicus Mapk1 116590 Gene mRNA down-regulation NA NA qRT-PCR; Western Blot etc. yes "Similarly, the protein level of ERK1/2 was significantly downregulated, while that of p-ERK1/2 was significantly upregulated in BLM-induced pulmonary fibrosis rats. NFE (400 and 200 mg/kg) treatment significantly and dose-dependently normalized the phosphorylation of ERK1/2, upregulated ERK1/2 protein levels, and downregulated p-ERK1/2 protein levels." 33953686 Effects of?Nervilia fordii?Extract on Pulmonary Fibrosis Through TGF-beta/Smad Signaling Pathway 2021 lung pulmonary_fibrosis mus_musculus Tgfbr2 21813 Gene mRNA up-regulation NA NA qRT-PCR; Western Blot; Immunohistochemistry etc. yes "Western blotting showed that TGF-beta1 promoted TGFBR2 expression, which was suppressed by atractylon treatment." 33855682 Atractylon Treatment Attenuates Pulmonary Fibrosis via Regulation of the mmu_circ_0000981/miR-211-5p/TGFBR2 Axis in an Ovalbumin-Induced Asthma Mouse Model 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens ASS1 445 Gene mRNA down-regulation NA NA qRT-PCR; Immunofluorescence; Flow Cytometry Assay etc. no "Compared to normal lung tissues, low ASS1 was detected in 73% (n =22/30) of ILD specimens (p < 0.0001). Likewise, a decline of ASS1 signal was found in the tissue sections from IPF patients, whereas more intense ASS1 staining was observed in normal lung tissues." 33508432 Therapeutic targeting of argininosuccinate synthase 1 (ASS1)-deficient pulmonary fibrosis 2021 lung silicosis mus_musculus E2f1 13555 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "RT-qRT-PCR analysis revealed a significantly increased E2F1 expression pattern in silicosis, which was highly positively correlated with the expression pattern of SKP2." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Skp2 27401 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "To further verify whether SKP2 was elevated in early silicosis, we analysed the SKP2 mRNA levels in the afore-mentioned tissues by RT-qRT-PCR and confirmed the presence of a significantly increased SKP2 expression pattern in the alveolar tissues of early silicosis." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Ambra1 228361 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "Taken together, these results revealed the upregulated expression of Beclin1 in silicosis, which may be attributed to the lung self-protective mechanism." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Col1a1 12842 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "The expression patterns of the collagen genes collagen type I alpha 1 (Col1a1) and Col3a1 in the alveolar tissues were determined by RT-qRT-PCR, and the Col1a1 and Col3a1 mRNA levels were significantly increased in the alveolar tissues of CS-treated mice." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Col3a1 12825 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "The expression patterns of the collagen genes collagen type I alpha 1 (Col1a1) and Col3a1 in the alveolar tissues were determined by RT-qRT-PCR, and the Col1a1 and Col3a1 mRNA levels were significantly increased in the alveolar tissues of CS-treated mice." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Map1lc3a 66734 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "Our findings revealed that the mRNA and protein levels of Beclin1, LC3 and autophagy-related gene-5 (ATG5) were increased after treatment with CS, and Beclin1, LC3 and ATG5 increased upon combination treatment with CS and rapamycin." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung silicosis mus_musculus Atg5 11793 Gene mRNA up-regulation NA NA Immunohistochemistry; qRT-PCR; Western Blot etc. no "Our findings revealed that the mRNA and protein levels of Beclin1, LC3 and autophagy-related gene-5 (ATG5) were increased after treatment with CS, and Beclin1, LC3 and ATG5 increased upon combination treatment with CS and rapamycin." 34428336 MicroRNA-205-5p targets E2F1 to promote autophagy and inhibit pulmonary fibrosis in silicosis through impairing SKP2-mediated Beclin1 ubiquitination 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Yap1 22601 Gene mRNA up-regulation NA NA Western Blot; Immunofluorescence etc. no "The expression of YAP, Smad-3 and p21 were significantly increased in AECs of IPF mice compared to normal mice." 33994367 Efficacy of YAP1-gene Knockdown to Inhibit Alveolar-Epithelial-Cell Senescence and Alleviate Idiopathic Pulmonary Fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Smad3 17127 Gene mRNA up-regulation NA NA Western Blot; Immunofluorescence etc. no "The expression of YAP, Smad-3 and p21 were significantly increased in AECs of IPF mice compared to normal mice." 33994367 Efficacy of YAP1-gene Knockdown to Inhibit Alveolar-Epithelial-Cell Senescence and Alleviate Idiopathic Pulmonary Fibrosis (IPF) 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Cdkn1a 12575 Gene mRNA up-regulation NA NA Western Blot; Immunofluorescence etc. no "The expression of YAP, Smad-3 and p21 were significantly increased in AECs of IPF mice compared to normal mice." 33994367 Efficacy of YAP1-gene Knockdown to Inhibit Alveolar-Epithelial-Cell Senescence and Alleviate Idiopathic Pulmonary Fibrosis (IPF) 2021 lung respiratory_distress_syndrome_acute homo_sapiens BCL2 596 Gene mRNA up-regulation NA NA Western Blot; qRT-PCR etc. no "Western blotting and RT-qRT-PCR results showed that Bcl-2 expressions increased significantly after LPS stimulation in the LPS group as compared with the blank control group, and caspase-3 expressions decreased significantly." 34412758 Overexpression of mitofusion 2 inhibits acute respiratory distress syndrome pulmonary fibrosis and its mechanism 2021 lung respiratory_distress_syndrome_acute homo_sapiens CASP3 836 Gene mRNA down-regulation NA NA Western Blot; qRT-PCR etc. no "Western blotting and RT-qRT-PCR results showed that Bcl-2 expressions increased significantly after LPS stimulation in the LPS group as compared with the blank control group, and caspase-3 expressions decreased significantly." 34412758 Overexpression of mitofusion 2 inhibits acute respiratory distress syndrome pulmonary fibrosis and its mechanism 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens GREM2 64388 Gene mRNA up-regulation NA NA Immunohistochemistry; Immunofluorescence; qRT-PCR etc. no Gremlin2 was highly expressed in the serum and lung tissues in IPF patients. Bleomycin-induced lung fibrosis model exhibited high expression of Gremlin2 in the bronchoalveolar lavage fluid (BALF) and lung tissue. 34422900 Gremlin2 Activates Fibroblasts to Promote Pulmonary Fibrosis Through the Bone Morphogenic Protein Pathway 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Grem2 23893 Gene mRNA up-regulation NA NA Immunohistochemistry; Immunofluorescence; qRT-PCR etc. no "Compared with the commonly used fibrosis indexes involving collagen1 (Col1) and fibronectin (FN), we found that the Gremlin2 expression level in the fibrosis model mice group increased more significantly, and was even more sensitive and indicative than the international indexes." 34422900 Gremlin2 Activates Fibroblasts to Promote Pulmonary Fibrosis Through the Bone Morphogenic Protein Pathway 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SPP1 6696 Gene mRNA up-regulation NA NA Histological Analysis; qRT-PCR etc. no "Osteopontin (OPN), a matricellular protein with proinflammatory and profibrotic properties, plays a major role in several fibrotic diseases, including IPF; OPN is highly upregulated in patients' lung samples." 34243624 Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Spp1 20750 Gene mRNA up-regulation NA NA Histological Analysis; qRT-PCR etc. no OPN expression increased significantly in the BLM-injected mouse groups compared to that in the control group. 34243624 Osteopontin silencing attenuates bleomycin-induced murine pulmonary fibrosis by regulating epithelial-mesenchymal transition 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Tnf 21926 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "Firstly, we found that the lung expression levels of Tnf (the gene encoding TNF-alfa) and Il1b (the gene encoding IL-1beta) were higher in BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Il1b 16176 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "Firstly, we found that the lung expression levels of Tnf (the gene encoding TNF-alfa) and Il1b (the gene encoding IL-1beta) were higher in BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Tgfb1 21803 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "The pulmonary expression of all tested genes-Tgfb1?(coding for TGFbeta),?Acta2 (coding for alfa-SMA),?Col1a1?(coding for collagen) and?Fn1?(coding for fibronectin)-was greater in the BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Acta2 11475 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "The pulmonary expression of all tested genes-Tgfb1?(coding for TGFbeta),?Acta2 (coding for alfa-SMA),?Col1a1?(coding for collagen) and?Fn1?(coding for fibronectin)-was greater in the BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Col1a1 12842 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "The pulmonary expression of all tested genes-Tgfb1?(coding for TGFbeta),?Acta2 (coding for alfa-SMA),?Col1a1?(coding for collagen) and?Fn1?(coding for fibronectin)-was greater in the BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Fn1 14268 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "The pulmonary expression of all tested genes-Tgfb1?(coding for TGFbeta),?Acta2 (coding for alfa-SMA),?Col1a1?(coding for collagen) and?Fn1?(coding for fibronectin)-was greater in the BLM-treated mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Cdh1 12550 Gene mRNA down-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "Indeed, the lung tissue expression of genes coding for epithelial cell markers (such as?Cdh1?coding for E-cadherin and?Ocln?coding for occludin) was significantly lower in BLM mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Ocln 18260 Gene mRNA down-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes "Indeed, the lung tissue expression of genes coding for epithelial cell markers (such as?Cdh1?coding for E-cadherin and?Ocln?coding for occludin) was significantly lower in BLM mice than in control animals." 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Muc5b 74180 Gene mRNA up-regulation NA NA Immunofluorescence; qRT-PCR; Western Blot etc. yes We also found that mRNA expression of MUC5B (encoded by?Muc5b)?in the lung was significantly greater in BLM-treated mice than in control animals. 34529707 GED-0507 attenuates lung fibrosis by counteracting myofibroblast transdifferentiation in vivo and in vitro 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens SOX9 6662 Gene mRNA up-regulation NA NA Immunohistochemistry; Immunofluorescence; Western Blot etc. no "Furthermore, measurement of?SOX9?transcript levels revealed a significant increase in the total lung transcripts of?SOX9?in individuals with IPF compared with those in healthy controls." 34520400 Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis mus_musculus Sox9 20682 Gene mRNA up-regulation NA NA Immunohistochemistry; Immunofluorescence; Western Blot etc. no We demonstrate that Sox9 is upregulated via MAPK/PI3K-dependent signaling and by the transcription factor Wilms' tumor 1 in distal lung-resident fibroblasts in IPF. 34520400 Dysregulated overexpression of Sox9 induces fibroblast activation in pulmonary fibrosis 2021 lung idiopathic_pulmonary_fibrosis homo_sapiens EIF4EBP1 1978 Gene mRNA up-regulation NA mTOR pathway Western Blot; qRT-PCR; Immunofluorescence etc. yes "The analysis showed that the transcript levels of genes in the mTOR pathway, including?EIF4EBP1, MAP1LC3A?and?RPS6,?were positively correlated with fibrotic lesions. Interestingly, the transcript levels of the autophagy gene?ATG5, which is negatively regulated by mTOR, were negatively correlated with IPF." 35159160 Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens MAP1LC3A 84557 Gene mRNA up-regulation NA mTOR pathway Western Blot; qRT-PCR; Immunofluorescence etc. yes "The analysis showed that the transcript levels of genes in the mTOR pathway, including?EIF4EBP1, MAP1LC3A?and?RPS6,?were positively correlated with fibrotic lesions. Interestingly, the transcript levels of the autophagy gene?ATG5, which is negatively regulated by mTOR, were negatively correlated with IPF." 35159160 Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens RPS6 6194 Gene mRNA up-regulation NA mTOR pathway Western Blot; qRT-PCR; Immunofluorescence etc. yes "The analysis showed that the transcript levels of genes in the mTOR pathway, including?EIF4EBP1, MAP1LC3A?and?RPS6,?were positively correlated with fibrotic lesions. Interestingly, the transcript levels of the autophagy gene?ATG5, which is negatively regulated by mTOR, were negatively correlated with IPF." 35159160 Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens ATG5 9474 Gene mRNA down-regulation NA mTOR pathway Western Blot; qRT-PCR; Immunofluorescence etc. yes "The analysis showed that the transcript levels of genes in the mTOR pathway, including?EIF4EBP1, MAP1LC3A?and?RPS6,?were positively correlated with fibrotic lesions. Interestingly, the transcript levels of the autophagy gene?ATG5, which is negatively regulated by mTOR, were negatively correlated with IPF." 35159160 Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens CHIT1 1118 Gene mRNA up-regulation NA NA Chitotriosidase Assay; YKL-40 Assay etc. yes "This explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response." 35222369 Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis 2022 lung idiopathic_pulmonary_fibrosis homo_sapiens CHI3L1 1116 Gene mRNA up-regulation NA NA Chitotriosidase Assay; YKL-40 Assay etc. yes "This explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response." 35222369 Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis 2022 lung pulmonary_fibrosis mus_musculus Col1a1 12824 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of several fibrotic genes, Col1A1, CTGF, MMP2, Acta2 and TGFbeta1 was increased by 3.15 +- 0.83-, 1.74 +- 0.24-, 2.3 +- 0.19-, 1.91 +- 0.36 and 3.44 +- 0.39 (P < 0.05)-fold, respectively, in lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Ccn2 14219 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of several fibrotic genes, Col1A1, CTGF, MMP2, Acta2 and TGFbeta1 was increased by 3.15 +- 0.83-, 1.74 +- 0.24-, 2.3 +- 0.19-, 1.91 +- 0.36 and 3.44 +- 0.39 (P < 0.05)-fold, respectively, in lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Mmp2 17390 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of several fibrotic genes, Col1A1, CTGF, MMP2, Acta2 and TGFbeta1 was increased by 3.15 +- 0.83-, 1.74 +- 0.24-, 2.3 +- 0.19-, 1.91 +- 0.36 and 3.44 +- 0.39 (P < 0.05)-fold, respectively, in lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Acta2 11475 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of several fibrotic genes, Col1A1, CTGF, MMP2, Acta2 and TGFbeta1 was increased by 3.15 +- 0.83-, 1.74 +- 0.24-, 2.3 +- 0.19-, 1.91 +- 0.36 and 3.44 +- 0.39 (P < 0.05)-fold, respectively, in lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Tgfb1 21803 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of several fibrotic genes, Col1A1, CTGF, MMP2, Acta2 and TGFbeta1 was increased by 3.15 +- 0.83-, 1.74 +- 0.24-, 2.3 +- 0.19-, 1.91 +- 0.36 and 3.44 +- 0.39 (P < 0.05)-fold, respectively, in lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Il6 16193 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of proinflammatory cytokine genes; IL6, IL1beta and RelA were increased by 2.52 +- 0.31-, 2.32 +- 0.06 and 3.01 +- 0.5 (P < 0.05)-fold, respectively, in the lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Il1b 16176 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of proinflammatory cytokine genes; IL6, IL1beta and RelA were increased by 2.52 +- 0.31-, 2.32 +- 0.06 and 3.01 +- 0.5 (P < 0.05)-fold, respectively, in the lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Rela 19697 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of proinflammatory cytokine genes; IL6, IL1beta and RelA were increased by 2.52 +- 0.31-, 2.32 +- 0.06 and 3.01 +- 0.5 (P < 0.05)-fold, respectively, in the lungs of BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Bmpr1a 12166 Gene mRNA down-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of BMPR1A, Cav1 and Edn1 genes were reduced by 0.27 +- 0.04, 0.18 +- 0.804 and 0.95 +- 0.1-fold (P < 0.05), respectively, in BLM-treated WT mice, compared to untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Cav1 12389 Gene mRNA down-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of BMPR1A, Cav1 and Edn1 genes were reduced by 0.27 +- 0.04, 0.18 +- 0.804 and 0.95 +- 0.1-fold (P < 0.05), respectively, in BLM-treated WT mice, compared to untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Edn1 13614 Gene mRNA down-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of BMPR1A, Cav1 and Edn1 genes were reduced by 0.27 +- 0.04, 0.18 +- 0.804 and 0.95 +- 0.1-fold (P < 0.05), respectively, in BLM-treated WT mice, compared to untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Pecam1 18613 Gene mRNA down-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "The mRNA expression of BMPR1A, Cav1 and Edn1 genes were reduced by 0.27 +- 0.04, 0.18 +- 0.804 and 0.95 +- 0.1-fold (P < 0.05), respectively, in BLM-treated WT mice, compared to untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 lung pulmonary_fibrosis mus_musculus Bak1 12018 Gene mRNA up-regulation NA NA qRT-PCR; Microarray Analysis etc. yes "Expression of the pro-apoptotic Bcl2 family gene, Bak is increased by 2.31 +- 0.30-fold in BLM-treated WT mice, compared with the untreated WT mice." 35083615 Inhibition of nuclear factor kappaB in the lungs protect bleomycin-induced lung fibrosis in mice 2022 heart myocardial_infarction mus_musculus Prkaa1 105787 Gene mRNA down-regulation Cx43 NA NA no Prkaa1 influences Cx43 expression by both a transcriptional and a post-transcriptional mechanism involving miR-125b-5p. 33564961 AMPK-alpha1 deletion in myofibroblasts exacerbates post-myocardial infarction fibrosis by a connexin 43 mechanism 2021 heart lipotoxic_cardiomyopathy rattus_norvegicus Hmgcs2 24450 Gene mRNA up-regulation NA NA NA no "Exercise-mediated cardioprotection by upregulating miR-344g-5p, which targets Hmgcs2 mRNA, prohibits HMGCS2 upregulation and thus lipotoxicity." 32826638 Exercise Training Reverses Lipotoxicity-induced Cardiomyopathy by Inhibiting HMGCS2 2021 heart myocardial_infarction mus_musculus Klf5 12224 Gene mRNA down-regulation mir-27a TGF-BETA SIGNALING PATHWAY bioinformatic analyses;luciferase assays no KLF5 possibly induces cell and tissue damage in myocardial infarction through downregulation of miR-27a and the subsequent activation of GFPT2/TGF-beta/Smad2/3 axis. 33910455 Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-beta/Smad2/3 axis activation 2021 heart myocardial_infarction homo_sapiens KLF5 688 Gene mRNA down-regulation mir-27a TGF-BETA SIGNALING PATHWAY bioinformatic analyses;luciferase assays no KLF5 possibly induces cell and tissue damage in myocardial infarction through downregulation of miR-27a and the subsequent activation of GFPT2/TGF-beta/Smad2/3 axis. 33910455 Promoting roles of KLF5 in myocardial infarction in mice involving microRNA-27a suppression and the following GFPT2/TGF-beta/Smad2/3 axis activation 2021 heart endomyocardial_fibrosis rattus_norvegicus Dnmt1 84350 Gene mRNA methylation miR-152-3p WNT SIGNALING PATHWAY NA no DNMT1 methylation regulates miR-152-3p to slow the progression of cardiac fibrosis by inhibiting the Wnt1/beta-catenin pathway. 34424481 DNMT1-Induced miR-152-3p Suppression Facilitates Cardiac Fibroblast Activation in Cardiac Fibrosis 2021 heart endomyocardial_fibrosis mus_musculus Rgs4 19736 Gene mRNA up-regulation NA TGF-BETA SIGNALING PATHWAY qRT-PCR;western blot;Masson staining no RGS4 promoted cardiac fibrosis and attenuated the anti-cardiac fibrosis of choline. RGS4 may weaken anti-cardiac fibrosis of choline through TGF-BETA1/Smad and MAPK signaling pathways. 33892733 The association between RGS4 and choline in cardiac fibrosis 2021 heart diabetic_cardiomyopathy homo_sapiens KLK8 11202 Gene mRNA up-regulation NA TGF-BETA SIGNALING PATHWAY NA no "KLK8 overexpression led to plakoglobin-dependent association of p53 with hypoxia inducible factor (HIF)-1alpha, which further enhanced the transactivation effect of HIF-1alpha on the TGF-beta1 promoter. KLK8 also induced the binding of p53 with Smad3, subsequently promoting pro-EndMT reprogramming via the TGF-beta1/Smad signaling pathway in human coronary artery endothelial cells." 33754057 A novel role of kallikrein-related peptidase 8 in the pathogenesis of diabetic cardiac fibrosis 2021 heart endomyocardial_fibrosis mus_musculus Adam17 11491 Gene mRNA up-regulation NA NA qRT-PCR;CCK-8 assays;western blot etc. yes "ADAM17 expression plays a key role in cardiac fibrosis by regulating endoplasmic reticulum stress and mitophagy, thereby limiting fibrosis and improving heart function." 34035876 The Downregulation of ADAM17 Exerts Protective Effects against Cardiac Fibrosis by Regulating Endoplasmic Reticulum Stress and Mitophagy 2021 heart endomyocardial_fibrosis homo_sapiens E2F1 1869 Gene mRNA up-regulation CCNE2 NA luciferase report assay;immunoprecipitation no "E2F1 and its downstream target gene CCNE2 play a vital role in TGF-beta1-induced HCFs differentiation, thus E2F1 and CCNE2 may be a potential therapeutic target for cardiac fibrosis." 34521301 E2F transcription factor 1 (E2F1) promotes the transforming growth factor TGF-beta1 induced human cardiac fibroblasts differentiation through promoting the transcription of CCNE2 gene 2021 kidney nephrolithiasis homo_sapiens CXCR4 7852 Gene mRNA up-regulation NA NF-KAPPA B SIGNALING PATHWAY RNA sequencing;qRT-PCR;immunohistochemistry etc. no CXCR4 inhibition attenuates CaOx crystal deposition-induced renal fibrosis by suppressing autophagy and EMT through the NF-kB pathway. 35255299 CXCR4 inhibition attenuates calcium oxalate crystal deposition-induced renal fibrosis 2022 kidney nephrolithiasis mus_musculus Cxcr4 12767 Gene mRNA up-regulation NA NF-KAPPA B SIGNALING PATHWAY RNA sequencing;qRT-PCR;immunohistochemistry etc. no CXCR4 inhibition attenuates CaOx crystal deposition-induced renal fibrosis by suppressing autophagy and EMT through the NF-kB pathway. 35255299 CXCR4 inhibition attenuates calcium oxalate crystal deposition-induced renal fibrosis 2022 kidney chronic_kidney_disease mus_musculus Lmcd1 30937 Gene mRNA up-regulation NA NA NA no Inhibition of LMCD1 protects against renal interstitial fibrosis by impeding ERK activation. 34968577 Suppression of LMCD1 ameliorates renal fibrosis by blocking the activation of ERK pathway 2022 kidney chronic_kidney_disease homo_sapiens LMCD1 2995 Gene mRNA up-regulation NA NA NA no Inhibition of LMCD1 protects against renal interstitial fibrosis by impeding ERK activation. 34968577 Suppression of LMCD1 ameliorates renal fibrosis by blocking the activation of ERK pathway 2022