MicroRNA-146b-3p regulates the dysfunction of vascular smooth muscle cells via repressing phosphoinositide-3 kinase catalytic subunit gamma

MicroRNA-146b-3p通过抑制磷酸肌醇-3激酶催化亚基γ调控血管平滑肌细胞功能障碍

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作者:Xijing Zhuang, Feng Gao, Lei Shi, Wei Liu, Wenjun Wang, Xuezhi He, Yang Gao

Abstract

MicroRNAs are crucial regulators in the phenotype switch of vascular smooth muscle cells (VSMCs). Nonetheless, the role of miR-146b-3p in VSMCs remains unclear. In the present study, platelet-derived growth factor-BB (PDGF-BB) at different concentrations was employed to stimulate VSMCs for different times, to establish the model of VSMC dysfunction. The relative expression of miR-146b-3p was quantified by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was measured by BrdU assay. Flow cytometry analysis was employed for the analysis of cell cycle. VSMC migration was detected by Transwell assay. Phosphoinositide-3 kinase catalytic subunit-gamma (PIK3CG) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC, and Calponin were examined employing Western blot. The targeting relationship between miR-146b-3p and PIK3CG 3'-UTR was affirmed by dual-luciferase gene assay. We report that the reduction of miR-146b-3p expression was induced by PDGF-BB in a time-dependent and dose-dependent manner (P < 0.05). The overexpression of miR-146b-3p counteracted the effects of PDGF-BB on the proliferation and migration of VSMCs and increased the expressions of differentiation markers (P < 0.05). Additionally, PIK3CG expression was negatively regulated by miR-146b-3p, and the restoration of PIK3CG partly eliminated the effects of miR-146b-3p on VSMCs (P < 0.05). In summary, miR-146b-3p represses the proliferation, migration, and phenotype switch of VSMCs induced by PDGF-BB via targeting PIK3CG. Therefore, miR-146b-3p/PIK3CG may be a potential target for the treatment of atherosclerosis.

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