MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo
MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo
复制标题
MicroRNA-204 在体外和体内调节血管平滑肌细胞钙化。
DOI：
10.1093/cvr/cvs258
复制
发表时间：
2012-11-01
影响因子：
10.8
通讯作者：
Liao, Er-Yuan
中科院分区：
文献类型：
--
作者：
Cui, Rong-Rong;Li, Shi-Jun;Liao, Er-Yuan
旨在
内侧动脉钙化是一种常见的大血管病，起源于类似骨生成的细胞调节过程。虽然这一过程的机制尚不清楚，但特定microRNA的表观基因组调控可能在血管平滑肌细胞（VSMC）钙化中发挥作用。本研究旨在探讨miR-204是否参与VSMC钙化的调控。
方法和结果
我们发现，在β-甘油磷酸诱导的钙化过程中，miR-204在小鼠主动脉VSMC中受到抑制，而Runx 2蛋白水平升高。通过转染miR-204模拟物过表达miR-204降低Runx 2蛋白水平并减轻β-甘油磷酸盐诱导的VSMC成骨分化，而通过转染miR-204抑制剂抑制miR-204显著升高Runx 2蛋白水平并增强VSMC的成骨分化，表明miR-204在VSMC钙化中作为Runx 2的内源性衰减剂的作用。荧光素酶报告基因分析显示Runx 2是miR-204的直接靶标，通过在VSMC中Runx 2的野生型或突变体3 '-UTR序列上过表达miR-204。通过在昆明小鼠中注射miR-204 agomir体内过表达miR-204减轻维生素D3诱导的中动脉钙化。
结论
我们的研究表明，miR-204的下调可能通过调节Runx 2参与β-甘油磷酸诱导的VSMC钙化。miR-204代表了VSMC钙化的重要新调节因子和中动脉钙化的潜在治疗靶点。
AIMS
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.
METHODS AND RESULTS
We found that miR-204 was suppressed in mouse aortic VSMCs during β-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 β-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.
CONCLUSION
Our study has shown that down-regulation of miR-204 may contribute to β-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.