Qian-ru Sun, Xiong Zhang, Kun Fang
(Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China (mainland))
Med Sci Monit 2018; 24:6599-6607
Phenotypic switch of vascular smooth muscle cells (VSMCs) participates in the etiology of various vascular diseases. It has been proved that microRNAs (miRNAs) serve as crucial regulators of functions of VSMCs. This study aimed to discover how miR-29b regulates the transformation of VSMCs phenotypes in mice.
MATERIAL AND METHODS: Primary VSMCs of aorta in mice were cultured in DMEM medium. A series of experiments involving transfection of oligonucleotides in cultured VSMCs, quantitative reverse transcription PCR (qRT-PCR), luciferase reporter assay, and Western blotting analysis were performed in this study.
RESULTS: We found that in VSMCs cultured in presence of stimulator, platelet-derived growth factor-BB (PDGF-BB), miR-29b was upregulated significantly and expressions of VSMC-phenotype-related genes (α-SMA, calponin, and SM-MHC) were regulated by miR-29b. Moreover, through downregulation of sirtuin 1 (SIRT1), miR-29b affects phenotypic transformation of VSMCs. Luciferase report assay identified a significant increase of SIRT1 3’-UTR activity in treatment with miR-29b inhibitor, which, however, was reversed in the presence of miR-29b mimic. Suppression of miR-29b reversed the activation of NF-κB induced by PDGF-BB in VSMCs.
CONCLUSIONS: We concluded that miR-29b is an important regulator in the PDGF-BB-mediated VSMC phenotypic transition by targeting SIRT1. Interventions aimed at miR-29b may be promising in treating numerous proliferative vascular disorders.
Keywords: Dementia, Vascular, Sex, sirtuin 1