Regulation of podocyte lesions in diabetic nephropathy via miR-34a in the Notch signaling pathway. Issue 44 (November 2016)

• Record Type: Journal Article
• Authors: Zhang, Xiangying; Song, Shuping; Luo, Huixin
• Editors: Lymperopoulos., Anastasios
• Is Part Of: Medicine. Volume 95:Issue 44(2016)
• Page Start: e5050
• Publication Date: 2016-11
• Subjects: diabetic nephropathy -- high glucose -- miR-34a -- Notch signaling pathway -- podocyte lesions; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000005050
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract: Background: The activation of the Notch signaling pathway has been shown to play an important role in diabetic nephropathy (DN) development. Besides, Notch-1 is a target gene in miR-34a. However, the regulation of the podocyte lesions involved in DN by miR-34a has not been identified. Methods: This study utilized miR-34a mimics and small interfering RNA transfection to construct miR-34a overexpression and lower-expression model to investigate the effect of miR-34a on the regulation of the Notch signaling pathway and podocyte lesions in DN. Western blotting and real-time quantitative polymerase chain reaction were applied for the quantitative testing of mRNA and protein expression. Apoptosis of podocyte was detected by TUNEL staining. Results: In high-glucose (HG) conditions, miR-34a overexpression inhibited the expression of Notch 1, Jagged 1, NICD, Hes 1, and Hey 1 proteins. Further, cleaved caspase-3, Bax, and phosphorylation of p53 (p-p53) were reduced significantly. Therefore, miR-34a overexpression inhibited the Notch signaling pathway and podocyte lesions induced by HG. β-arrestin was slightly reduced in HG conditions. Meanwhile, miR-34a overexpression could remit the inhibition. Conclusion: Results from this study provide evidence that miR-34a may offer a new approach for the treatment of diabetes.