Baicalin reversal of DNA hypermethylation-associated Klotho suppression ameliorates renal injury in type 1 diabetic mouse model. Issue 23 (1st December 2020)

• Record Type: Journal Article
• Authors: Zhang, Xiao-Tan; Wang, Guang; Ye, Liu-Fang; Pu, Yu; Li, Run-Tong; Liang, Jianxin; Wang, Lijun; Lee, Kenneth Ka Ho; Yang, Xuesong
• Is Part Of: Cell cycle. Volume 19:Issue 23(2020)
• Page Start: 3329
• Page End: 3347
• Publication Date: 2020-12-01
• Subjects: Diabetes -- kidney -- fibrosis -- DNA methylation -- Klotho; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2020.1843815
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: Baicalin is a flavone glycoside that possesses numerous pharmacological properties. but its protective mode of action in kidney injury induced by diabetes mellitus remains incompletely understood. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin could ameliorate diabetes-induced the pathological changes of the kidney function and morphology through suppressing inflammation and oxidative stress. Furthermore, baicalin treatment could alleviate interstitial fibrosis in the diabetic kidney via inhibiting epithelial-to-mesenchymal transition (EMT), which was accompanied by a sharp upregulation of Klotho, the endogenous inhibitor of renal fibrosis. We further verified that baicalin-rescued expression of Klotho was associated with Klotho promoter hypomethylation due to aberrant methyltransferase 3a expressions. Klotho knockdown via RNA interferences largely abrogated the anti-renal fibrotic effects of Baicalin in HK2 cells. These findings suggested that baicalin could alleviate renal injury-induced by diabates through partly modulating Klotho promoter methylation, which provides new insights into the treatment of diabetic nephropathy.