title: MicroRNA-492 reverses high glucose-induced insulin resistance in HUVEC cells through targeting resistin.
abstract: The development of atherosclerosis (AS) is a multifactorial process, in which elevated plasma resistin (a key factor leading to insulin resistance) levels play an important role. Emerging evidence indicate that microRNAs (miRNAs) are involved in AS; However, the regulation and function of miRNAs in response to AS remain poorly understood. Our study analyzed the effects of miR-492 on insulin resistance, endothelial activation, and resistin expression in apoE knock-out mice and human umbilical vein endothelial cells after high-glucose treatment and miR-492 mimics transfection. We also investigated the underlying molecular mechanisms. Our results showed that high glucose stress induced a significant decrease in miR-492 expression, with a remarkable upregulation of resistin expression. We then identified resistin as a novel direct target of miR-492 using 3'-UTR luciferase reporter assay. Histopathologic examination demonstrated that upregulation of miR-492 attenuated endothelial cells migration and lipid accumulation induced by high glucose stress. Further investigation demonstrated that the upregulation of p-STAT3, SOCS, and P-selectin activation induced by high glucose stress was attenuated by upregulation of miR-492. Together, our findings indicate that miR-492 contributes to insulin resistance and endothelial dysfunction induced by high glucose, via directly downregulating resistin expression, and involving STAT3 phosphorylation, SOCS, and P-selectin activation.
authors: Cardiac Rehabilitation Center, Department of Rehabilitation, Xiangya Hospital, Central South University, Xiang-Ya Road 87, Changsha, 41008, Hunan, People's Republic of China.
authors: Cai
authors: C
authors: Ying
authors: Liu
authors: L
authors: Sui-Xin
authors: Xie
authors: X
authors: Kang-Ling
authors: Zhang
authors: Z
authors: Wen-Liang
authors: Dong
authors: D
authors: Lei
authors: Liu
authors: L
authors: Yuan
authors: Zheng
authors: Z
authors: Fan
authors: Zhuo
authors: Z
authors: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D052243:Resistin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D007328:Insulin; C558125:MIRN492 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D052243:Resistin; D005947:Glucose