Insulin promotes vascular smooth muscle cell proliferation via microRNA-208-mediated downregulation of p21

• DOI: 10.1097/hjh.0b013e328348ef8e
• Publication Date: 2011-07-04T12:03:35Z
• Authors: Ye Zhang; Yan Wang; Xukai Wang; Yi Zhang; Gilbert M. Eisner; Laureano D. Asico; Pedro A. Jose; Chunyu Zeng
• Keywords: Cyclin-Dependent Kinase Inhibitor p21; 0301 basic medicine; 0303 health sciences; Dose-Response Relationship, Drug; Cell Cycle; Down-Regulation; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; MicroRNAs; 03 medical and health sciences; Models, Animal; Animals; Insulin; Aorta; Cells, Cultured; Cell Proliferation; Signal Transduction

Abnormal vascular smooth muscle cell (VSMC) proliferation is involved in the development of diseases. However, mechanisms by which insulin exerts this effect are not completely known. We hypothesize that microRNAs might be insulin-induced VSMC proliferation.VSMC was determined [H]-thymidine incorporation; were microRNA chips and real-time PCR; p21expression immunoblotting.In study, we found increased miR-208 expression. Overexpression basal insulin-mediated proliferation. Although a inhibitor, itself, had no on proliferation, it reduced Moreover, transformation cycle from G0/G1 phase to S phase. Bioinformatics analysis p21, member cyclin-dependent kinase (CDK)-inhibitory protein family, may target miR-208. Insulin decreased p21 expression VSMCs; transfection also In presence inhibitory VSMCs partially blocked. The interaction between direct. Using luciferase reporter with entire wild-type 3'UTR or mutant HEK293 cells, but neither mimic nor any significant activity.This study indicates miRNAs, miR-208, particular, via downregulation its potential target, key CDK-inhibitory family.