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• W2527768049 abstract "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." @default.
• W2527768049 created "2016-10-14" @default.
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• W2527768049 date "2016-10-05" @default.
• W2527768049 modified "2023-10-17" @default.
• W2527768049 title "Rhein reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal fibrosis in mice" @default.
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• W2527768049 doi "https://doi.org/10.1038/srep34597" @default.
• W2527768049 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5050540" @default.
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• W2527768049 hasPublicationYear "2016" @default.
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