期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 483, 期 1, 页码 318-324出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2016.12.145
关键词
Diabetic nephropathy; miR-217; Podocyte injury; Insulin resistance; Autophagy; PTEN
资金
- Humanities and Social Sciences Research Projects of Education Bureau of Henan Province [2017-ZZJH-439]
- Support Project for the Disciplinary Group of Psychology and Neuroscience, Xinxiang Medical University
Podocyte damage is the initial hallmark of diabetic nephropathy (DN), leading to the increasing morbidity and mortality in diabetic patients. Recent researches have corroborated the critical roles of miRNAs in the pathological progression of DN. Here, elevation of miR-217 was verified in high glucose (HG)-stimulated podocytes. Moreover, blocking miR-217 expression antagonized HG-induced cell injury by attenuating the adverse role of HG on cell viability and inhibiting ROS levels and cell apoptosis. Simultaneously, miR-217 repression restored HG-disrupted insulin resistance by elevating glucose uptake and nephrin expression, an essential component for insulin-induced glucose uptake. Mechanism assay substantiated the defective autophagy in HG-treated podocytes, which was resumed by miR-217 cessation. Importantly, suppressing autophagy pathway with 3-MA alleviated the protective roles of miR-217 down-regulation in podocyte injury and insulin resistance. Luciferase reporter analysis confirmed that PTEN was a target of miR-217 in podocytes. Additionally, blocking PTEN expression restrained autophagy restoration in miR-217-decreased cells. Furthermore, PTEN down-regulation attenuated the beneficial role of miR-217 suppression in HG-induced injury and insulin resistance. Together, this study manifests that miR-217inhibition can protectively antagonize HG-induced podocyte damage and insulin resistance by restoring the defective autophagy pathway via targeting PTEN, representing a novel and promising therapeutic target against diabetic nephropathy. (C) 2016 Elsevier Inc. All rights reserved.
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