Effect of microRNA‐141 on the development of diabetic nephropathy through regulating AKT/AMPK signaling pathway by targeting insulin receptor substrate 2

• Published in: Journal of cellular biochemistry Vol. 120; no. 5; pp. 8008 - 8015
• Main Authors: Li, Yang, Huang, Denggao, Zheng, Linlin, Cao, Hui, Fan, Zhongcheng
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2019
• Subjects: Adenosine kinase; Adenosine monophosphate; AKT protein; AMP; Apoptosis; Blood; Diabetes; Diabetes mellitus; Diabetic nephropathy; Flow cytometry; Insulin; insulin receptor substrate 2; Interleukins; Kinases; MicroRNAs; microRNA‐141; miRNA; Nephropathy; Patients; Peripheral blood; Polymerase chain reaction; protein kinase B/adenosine monophosphate protein kinase; Proteins; Ribonucleic acid; RNA; Signal transduction; Signaling; Substrates; Tumor necrosis factor; Tumor necrosis factor-TNF; insulin receptor substrate 2; protein kinase B/adenosine monophosphate protein kinase; diabetic nephropathy; microRNA-141
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28078

Objective The aim of this study was to explore the effect of microRNA‐141 (miR‐141) on the development of diabetic nephropathy (DN) and its potential mechanism. Methods Real‐time quantitative polymerase chain reaction (RT‐qPCR) was used to detect the expression level of miR‐141 in peripheral blood of DN patients. Cell apoptosis was measured by flow cytometry. The expression levels of tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) were detected by enzyme‐linked immunosorbent assay. The expression level of insulin receptor substrate 2 (IRS2) was analyzed by RT‐qPCR and Western blot analysis. The targeting regulatory sites were predicted by Targetscan and luciferase assay was conducted to confirm the relationship between miR‐141 and IRS2. The expression levels of protein kinase B (AKT)/adenosine monophosphate protein kinase (AMPK)‐related proteins were investigated by Western blot analysis. Results MiR‐141 was upregulated in peripheral blood of DN patients (P < 0.05). Upregulation of miR‐141 significantly promoted apoptosis ( P < 0.05) and the expression of TNF‐α and IL‐6 ( P < 0.05). However, downregulation of miR‐141 inhibited cell apoptosis ( P < 0.05) and productions of TNF‐α and IL‐6 ( P < 0.05). Moreover, miR‐141 displayed a negatively regulatory effect on IRS2 abundance, and overexpression of IRS2 reversed the inhibitory effect of miR‐141 on development of DN cells ( P < 0.05). Besides, knockdown of miR‐141 significantly promoted the expressions of AKT/AMPK‐related proteins ( P < 0.05), which was attenuated by inhibition of IRS2 ( P < 0.05). Conclusion MiR‐141 promoted DN progression through regulating AKT/AMPK signaling pathway by targeting IRS2. MiR‐141 could regulate AKT/AMPK signaling pathway and promote DN progression by targeting IRS2 gene.