期刊
CARDIOVASCULAR RESEARCH
卷 96, 期 2, 页码 320-329出版社
OXFORD UNIV PRESS
DOI: 10.1093/cvr/cvs258
关键词
miR-204; Vascular smooth muscle cells; Calcification; Runx2
资金
- China National Natural Scientific Foundation [81000313, 30900622, 81070246, 30801174]
- Ministry of Education [078202042]
- Central South University 'Excellent Doctoral Dissertation of training support program'
Medial artery calcification is a common macroangiopathy that initiates from a cell-regulated process similar to osteogenesis. Although the mechanisms governing this process remain unclear, epigenomic regulation by specific microRNAs might play a role in vascular smooth muscle cell (VSMC) calcification. In this study, we aimed to investigate whether miR-204 participates in the regulation of VSMC calcification. We found that miR-204 was suppressed in mouse aortic VSMCs during -glycerophosphate-induced calcification, whereas Runx2 protein levels were elevated. Overexpression of miR-204 by transfection of miR-204 mimics decreased Runx2 protein levels and alleviated -glycerophosphate-induced osteoblastic differentiation of VSMCs, whereas miR-204 inhibition by transfection of miR-204 inhibitors significantly elevated Runx2 protein levels and enhanced osteoblastic differentiation of VSMCs, suggesting the role of miR-204 as an endogenous attenuator of Runx2 in VSMC calcification. Luciferase reporter assays revealed Runx2 as the direct target of miR-204 by overexpression of miR-204 on the wild-type or mutant 3-UTR sequences of Runx2 in VSMCs. In vivo overexpression of miR-204 by injection of miR-204 agomirs in Kunming mice attenuated vitamin D3-induced medial artery calcification. Our study has shown that down-regulation of miR-204 may contribute to -glycerophosphate-induced VSMC calcification through regulating Runx2. miR-204 represents an important new regulator of VSMC calcification and a potential therapeutic target in medial artery calcification.
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