Hsa-miR-199b-3p Prevents the Epithelial-Mesenchymal Transition and Dysfunction of the Renal Tubule by Regulating E-cadherin through Targeting KDM6A in Diabetic Nephropathy. (28th June 2021)

• Record Type: Journal Article
• Authors: Bai, Shoujun; Xiong, Xiaoyan; Tang, Bo; Ji, Tingting; Li, Xiaoying; Qu, Xiaolei; Li, Weiliang
• Other Names: Chen Shao Yu Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2021(2021)
• Publication Date: 2021-06-28
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2021/8814163
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. The association between epithelial-mesenchymal transition (EMT) and fibrosis is quite ascertained, but its link to eventual tubule dysfunction is missing. Here, we show that human microRNA- (hsa-miR-) 199b-3p protects renal tubules from diabetic-induced injury by repressing KDM6A, a histone lysine demethylase regulating E-cadherin expression. Lower E-cadherin expression is related to a higher level of KDM6A, while E-cadherin is promoted upon treatment with the KDM6A inhibitor GSK-J4 in both high glucose- (HG-) induced HK2 cells and the kidneys from streptozotocin- (STZ-) induced type 1 diabetic mice. However, overexpression or RNA silencing of E-cadherin fails to alter KDM6A expression. We also show that the upregulation of KDM6A is associated with the increased methylation level of the E-cadherin promoter. Then, the target prediction results and a dual-luciferase assay show that hsa-miR-199b-3p is a new miRNA that targets KDM6A. Overexpression of hsa-miR-199b-3p increases E-cadherin expression and prevents EMT through repressing KDM6A expression in HG-induced HK2 cells. In contrast, inhibitor-induced hsa-miR-199b-3p knockdown has opposite effects, as it decreases E-cadherin level and worsens EMT, accompanied by increased levels of KDM6A. Besides, Mir199b-knockout mice without mmu-miR-119b-3p expression exhibit more renal tubule dysfunction and more serious kidney tissue damage upon treatment with STZ. These results demonstrate that hsa-miR-199b-3p improves E-cadherin expression and prevents the progression of DN through targeting KDM6A. miR-199b-3p could be a future biomarker or target for the diagnosis or treatment of DN.