ArticleKidney international2014
Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic db/db mice.
Article in Kidney international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 129 citations in OpenAlex.
- Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction.Addiction biology · 2026Review
- Histone methylation of kidney disease: fact or fantasy?Renal failure · 2025Review
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src.Chinese medicine · 2025Article
- Epigenetic DNA Methylation and Protein Homocysteinylation: Key Players in Hypertensive Renovascular Damage.International journal of molecular sciences · 2024Review
- Evolution and global research trends of immunity in diabetic nephropathy: a bibliometric and visual analysis from 2004 to 2023.International urology and nephrology · 2024Article
- Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?Physiological reports · 2024Review
- Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression.International journal of molecular sciences · 2024Review
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?Life (Basel, Switzerland) · 2023Review
- Functioning and mechanisms of PTMs in renal diseases.Frontiers in pharmacology · 2023Review
- Advanced glycation end products regulate the receptor of AGEs epigenetically.Frontiers in cell and developmental biology · 2023Article
- Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives.International journal of molecular sciences · 2022Review
- On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics.Biomedicines · 2022Review
- Protein Methylation in Diabetic Kidney Disease.Frontiers in medicine · 2022Review
- Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis.International journal of molecular sciences · 2021Review
- Unraveling the epigenetic landscape of glomerular cells in kidney disease.Journal of molecular medicine (Berlin, Germany) · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Epigenetic mechanisms such as chromatin histone H3 lysine methylation and acetylation have been implicated in diabetic vascular complications. However, histone modification profiles at pathologic genes associated with diabetic nephropathy in vivo and their regulation by the angiotensin II type 1 receptor (AT1R) are not clear. Here we tested whether treatment of type 2 diabetic db/db mice with the AT1R blocker losartan not only ameliorates diabetic nephropathy, but also reverses epigenetic changes. As expected, the db/db mice had increased blood pressure, mesangial hypertrophy, proteinuria, and glomerular expression of RAGE and PAI-1 vs. control db/+ mice. This was associated with increased RNA polymerase II recruitment and permissive histone marks as well as decreased repressive histone marks at these genes, and altered expression of relevant histone modification enzymes. Increased MCP-1 mRNA levels were not associated with such epigenetic changes, suggesting post-transcriptional regulation. Losartan attenuated key parameters of diabetic nephropathy and gene expression, and reversed some but not all the epigenetic changes in db/db mice. Losartan also attenuated increased H3K9/14Ac at RAGE, PAI-1, and MCP-1 promoters in mesangial cells cultured under diabetic conditions. Our results provide novel information about the chromatin state at key pathologic genes in vivo in diabetic nephropathy mediated in part by AT1R. Thus, combination therapies targeting epigenetic regulators and AT1R could be evaluated for more effective treatment of diabetic nephropathy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.