ArticleJournal of the American Society of Nephrology : JASN2016
The Histone Methyltransferase Enzyme Enhancer of Zeste Homolog 2 Protects against Podocyte Oxidative Stress and Renal Injury in Diabetes.
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 55 papers.
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Who cites it
55 citing papers in PubMed, 91 citations in OpenAlex.
- Molecular mechanisms and therapeutic strategies of glomerular cell senescence in diabetic kidney disease: from heterogeneity to precision intervention.Cellular and molecular life sciences : CMLS · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Histone methyltransferase EZH2 drives podocyte injury and senescence in diabetic nephropathy through STAT3 activation.Cellular and molecular life sciences : CMLS · 2026Article
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- lncRNA SNHG6 improves placental villous cell function in anArchives of medical science : AMS · 2026Article
- Review
- Biphasic actions of the adenosine A2a receptor antagonist istradefylline in mice with obstructive uropathy.Scientific reports · 2025Article
- Article
- S-nitrosylation of EZH2 alters PRC2 assembly, methyltransferase activity, and EZH2 stability to maintain endothelial homeostasis.Nature communications · 2025Article
- Beyond Redox Regulation: Novel Roles of TXNIP in the Pathogenesis and Therapeutic Targeting of Kidney Disease.The American journal of pathology · 2025Review
- Xanthohumol attenuates TXNIP-mediated renal tubular injury in vitro and in vivo diabetic models.Journal of natural medicines · 2025Article
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- Research Progress on Podocyte Pyroptosis in Diabetic Nephropathy.Current medicinal chemistry · 2025Review
- ER-α36 prevents high glucose-induced cellular senescence and apoptosis in renal tubular cell.Frontiers in endocrinology · 2025Article
- Histone methylation modification and diabetic kidney disease: Potential molecular mechanisms and therapeutic approaches (Review).International journal of molecular medicine · 2024Review
- Tribbles pseudokinase 3 promoted renal fibrosis by regulating the expression of DNA damage-inducible transcript 3 in diabetic nephropathy.Biomolecules & biomedicine · 2024Article
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- An Updated Review on the Significance of DNA and Protein Methyltransferases and De-methylases in Human Diseases: From Molecular Mechanism to Novel Therapeutic Approaches.Current medicinal chemistry · 2024Review
- ROS: Executioner of regulating cell death in spinal cord injury.Frontiers in immunology · 2024Review
- The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes.Biomedicines · 2023Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Epigenetic regulation of oxidative stress is emerging as a critical mediator of diabetic nephropathy. In diabetes, oxidative damage occurs when there is an imbalance between reactive oxygen species generation and enzymatic antioxidant repair. Here, we investigated the function of the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) in attenuating oxidative injury in podocytes, focusing on its regulation of the endogenous antioxidant inhibitor thioredoxin interacting protein (TxnIP). Pharmacologic or genetic depletion of EZH2 augmented TxnIP expression and oxidative stress in podocytes cultured under high-glucose conditions. Conversely, EZH2 upregulation through inhibition of its regulatory microRNA, microRNA-101, downregulated TxnIP and attenuated oxidative stress. In diabetic rats, depletion of EZH2 decreased histone 3 lysine 27 trimethylation (H3K27me3), increased glomerular TxnIP expression, induced podocyte injury, and augmented oxidative stress and proteinuria. Chromatin immunoprecipitation sequencing revealed H3K27me3 enrichment at the promoter of the transcription factor Pax6, which was upregulated on EZH2 depletion and bound to the TxnIP promoter, controlling expression of its gene product. In high glucose-exposed podocytes and the kidneys of diabetic rats, the lower EZH2 expression detected coincided with upregulation of Pax6 and TxnIP. Finally, in a gene expression array, TxnIP was among seven of 30,854 genes upregulated by high glucose, EZH2 depletion, and the combination thereof. Thus, EZH2 represses the transcription factor Pax6, which controls expression of the antioxidant inhibitor TxnIP, and in diabetes, downregulation of EZH2 promotes oxidative stress. These findings expand the extent to which epigenetic processes affect the diabetic kidney to include antioxidant repair.
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