ArticleScientific reports2016
Rhein reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal fibrosis in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Rhein alleviates acute pancreatitis by inhibiting TMAO-mediated inflammatory signaling pathways and reducing acinar cell injury.Journal of advanced research · 2026Article
- Rhein attenuates severe acute pancreatitis-associated intestinal injury through PPARγ regulating macrophage activation.Chinese medical journal · 2026Article
- Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments.Acta pharmaceutica Sinica. B · 2025Review
- The Role of DNA Methyltransferases in Urinary System Diseases.Cancer innovation · 2025Review
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- [Potential of early diagnosis and targeted therapy for Klotho protein in chronic kidney disease].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- A PDE1 inhibitor, vinpocetine, ameliorates epithelial-mesenchymal transition and renal fibrosis in adenine-induced chronic kidney injury in rats by targeting the DNMT1/Klotho/β-catenin/Snail 1 and MMP-7 pathways.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Anthraquinones fromDrug design, development and therapy · 2025Review
- Targeting alveolar epithelial cell metabolism in pulmonary fibrosis: Pioneering an emerging therapeutic strategy.Frontiers in cell and developmental biology · 2025Review
- Natural products in traditional Chinese medicine for renal fibrosis: a comprehensive review.Frontiers in pharmacology · 2025Review
- Hypermethylation leads to the loss of HOXA5, resulting in JAG1 expression and NOTCH signaling contributing to kidney fibrosis.Kidney international · 2024Article
- Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene.Medical oncology (Northwood, London, England) · 2024Article
- Article
- FGF23 and klotho at the intersection of kidney and cardiovascular disease.Nature reviews. Cardiology · 2024Review
- An In Situ Sustained-Release Chitosan Hydrogel to Attenuate Renal Fibrosis by Retaining Klotho Expression.Biomaterials research · 2024Article
- A potential link between fibroblast growth factor-23 and the progression of AKI to CKD.BMC nephrology · 2023Article
- Research Progress on the Positive and Negative Regulatory Effects of Rhein on the Kidney: A Review of Its Molecular Targets.Molecules (Basel, Switzerland) · 2022Review
- Inhibitory Effects of Rhein on Renal Interstitial Fibrosis via the SHH-Gli1 Signal Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Traditional Chinese Medicine in the Treatment of Chronic Kidney Diseases: Theories, Applications, and Mechanisms.Frontiers in pharmacology · 2022Review
- Rhein ameliorates transverse aortic constriction-induced cardiac hypertrophyFrontiers in pharmacology · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal fibrosis is the hallmark of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications. Rhein, a plant-derived anthraquinone, displays strong anti-fibrosis properties, but its protective mode of action remains incompletely understood. Here we explore the mechanism of Rhein anti-renal fibrosis by investigating its regulation of Klotho, a known renal anti-fibrotic protein whose suppression after renal injury reportedly involves aberrant DNA methylation. We report that Rhein is an impressive up-regulator of Klotho and it markedly reversed Klotho down-regulation in unilateral ureteral occlusion-induced fibrotic kidney. Further examinations revealed that Klotho loss in fibrotic kidney is associated with Klotho promoter hypermethylation due to aberrant methyltransferase 1 and 3a expressions. However, Rhein significantly corrected all these epigenetic alterations and subsequently alleviated pro-fibrotic protein expression and renal fibrosis, whereas Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Rhein, suggesting that Rhein epigenetic reversal of Klotho loss represents a critical mode of action that confers Rhein's anti- renal fibrotic functions. Altogether our studies uncover a novel hypomethylating character of Rhein in preventing Klotho loss and renal fibrosis, and demonstrate the efficacy of Klotho-targeted epigenetic intervention in potential treatment of renal fibrosis-associated kidney diseases.
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