title: Repression of miR-217 protects against high glucose-induced podocyte injury and insulin resistance by restoring PTEN-mediated autophagy pathway.
abstract: 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.
authors.affiliation: School of Nursing, Xinxiang Medical University, Xinxiang, Henan, 453003, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of International Education, Xin Xiang Medical University, Xinxiang, Henan, 453003, PR China.
authors.forename: Zhao Pin
authors.initials: ZP
authors.lastname: Li
authors.affiliation: School of Nursing, Xinxiang Medical University, Xinxiang, Henan, 453003, PR China.
authors.forename: Rui Qin
authors.initials: RQ
authors.lastname: Zhang
authors.affiliation: School of Nursing, Xinxiang Medical University, Xinxiang, Henan, 453003, PR China. Electronic address: huiminzhanghn@163.com.
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002470:Cell Survival; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C000591813:MIRN-217 microRNA, mouse; D008565:Membrane Proteins; D035683:MicroRNAs; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C113267:nephrin; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D005947:Glucose
keywords: Autophagy; Diabetic nephropathy; Insulin resistance; PTEN; Podocyte injury; miR-217