ArticleJournal of the American Society of Nephrology : JASN2016
Inhibition of SET Domain-Containing Lysine Methyltransferase 7/9 Ameliorates Renal Fibrosis.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- Magnesium Attenuates Renal Senescence and Fibrosis With Reduced DNA Damage Response and H3K4me3 Enrichment at the p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- SETD7 depletion enhances white adipose browning and ameliorates metabolic disorders in obese mice.Cell death and differentiation · 2026Article
- Overexpression of Thrombomodulin in Adipose-Derived Mesenchymal Stem Cells Reduces Thrombogenic Risk and Enhances Therapeutic Efficacy.Journal of the American Society of Nephrology : JASN · 2026Article
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- Epigenetic histone modifications in kidney disease and epigenetic memory.Clinical and experimental nephrology · 2025Review
- Setdb1 ablation in macrophages attenuates fibrosis in heart allografts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting MLL1/WDR5-Mediated Epigenetic Regulation Mitigates Peritoneal Fibrosis by Reducing p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Direct fibroblast reprogramming: an emerging strategy for treating organic fibrosis.Journal of translational medicine · 2025Review
- SETD7 Dual Role in Disease and Opportunities for Therapeutic Intervention: Current Perspectives.Journal of inflammation research · 2025Review
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
- Epigenetic Regulation of Ferroptosis in Chronic Kidney Disease: Mechanisms and Implications.Research (Washington, D.C.) · 2025Review
- Epigenetics of Hypertensive Nephropathy.Biomedicines · 2024Review
- Histone methylation modification and diabetic kidney disease: Potential molecular mechanisms and therapeutic approaches (Review).International journal of molecular medicine · 2024Review
- Impacts of Hyperglycemia on Epigenetic Modifications in Human Gingival Fibroblasts and Gingiva in Diabetic Rats.International journal of molecular sciences · 2024Article
- Selective activation of PPARα by pemafibrate mitigates peritoneal inflammation and fibrosis through suppression of NLRP3 inflammasome and modulation of inflammation.Scientific reports · 2024Article
- Role of Histone Modifications in Kidney Fibrosis.Medicina (Kaunas, Lithuania) · 2024Review
- Set7/9 aggravates ischemic brain injury via enhancing glutamine metabolism in a blocking Sirt5 manner.Cell death and differentiation · 2024Article
- To target or not to target? The role of DNA and histone methylation in bacterial infections.Epigenetics · 2023Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β1 activity results in methylation of lysine 4 of histone H3 (H3K4) through SET domain-containing lysine methyltransferase 7/9 (SET7/9) induction, which is important for the transcriptional activation of fibrotic genes in vitro. However, in vivo studies utilizing an experimental model of renal fibrosis are required to develop therapeutic interventions that target SET7/9. In this study, we investigated the signaling pathway of TGF-β1-induced SET7/9 expression and whether inhibition of SET7/9 suppresses renal fibrosis in unilateral ureteral obstruction (UUO) mice and kidney cell lines. Among the SET family, SET7/9 was upregulated on days 3 and 7 in UUO mice, and the upregulation was suppressed by TGF-β1 neutralizing antibody. TGF-β1 induced SET7/9 expression via Smad3 in normal rat kidney (NRK)-52E cells. In human kidney biopsy specimens from patients diagnosed with IgA nephropathy and membranous nephropathy, SET7/9 expression was positively correlated with the degree of interstitial fibrosis (r=0.59, P=0.001 in patients with IgA nephropathy; and r=0.58, P<0.05 in patients with membranous nephropathy). In addition, small interfering RNA-mediated knockdown of SET7/9 expression significantly attenuated renal fibrosis in UUO mice. Sinefungin, an inhibitor of SET7/9, also suppressed the expression of mesenchymal markers and extracellular matrix proteins and inhibited H3K4 mono-methylation (H3K4me1) in kidneys of UUO mice. Moreover, sinefungin had an inhibitory effect on TGF-β1-induced α-smooth muscle actin expression and H3K4me1 in both NRK-52E and NRK-49F cells. In conclusion, sinefungin, a SET7/9 inhibitor, ameliorates renal fibrosis by inhibiting H3K4me1 and may be a candidate therapeutic agent.
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