Tissue Disease Species symbol ID Platform Type Expression Target Pathway Method Drug Function PMID Title Year 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 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 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 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 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 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 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 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 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 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 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_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 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 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 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_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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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