miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration
miRNA-34a reduces neointima formation through inhibiting smooth muscle cell proliferation and migration
复制标题
miRNA-34a 通过抑制平滑肌细胞增殖和迁移来减少新内膜形成
DOI：
10.1016/j.yjmcc.2015.10.017
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发表时间：
2015-12-01
影响因子：
5
通讯作者：
Zhang, Li
中科院分区：
文献类型：
--
作者：
Chen, Qishan;Yang, Feng;Zhang, Li
Aims: We have recently reported that microRNA-34a (miR-34a) regulates vascular smooth muscle cell (VSMC) differentiation from stem cells in vitro and in vivo. However, little is known about the functional involvements of miR-34a in VSMC functions and vessel injury-induced neointima formation. In the current study, we aimed to establish the causal role of miR-34a and its target genes in VSMC proliferation, migration and neointima lesion formation.Methods and results: Various pathological stimuli regulate miR-34a expression in VSMCs through a transcriptional mechanism, and the P53 binding site is required for miR-34a gene regulation by these stimuli. miR-34a overexpression in serum-starved VSMCs significantly inhibited VSMC proliferation and migration, while knockdown of miR-34a dramatically promoted VSMC proliferation and migration, respectively. Notch homolog 1 (Notch1), a well-reported regulator in VSMC functions and arterial remodeling, was predicted as one of the top targets of miR-34a by using several computational miRNA target prediction tools, and was negatively regulated by miR34a in VSMCs. Luciferase assay showed miR-34a substantially repressed wild type Notch1-3'-UTR-luciferase activity in VSMCs, but not mutant Notch1-3'-UTR-luciferease reporter, confirming the Notch1 is the functional target of miR-34a in VSMCs. Data from co-transfection experiments also revealed that miR-34a inhibited VSMC proliferation and migration through modulating Notch gene expression levels. Importantly, the expression level of miR-34a was significantly down-regulated in injured arteries, and miR-34a perivascular overexpression significantly reduced Notch1 expression levels, decreased VSMC proliferation, and inhibited neointima formation in wire-injured femoral arteries.Conclusion: Our data have demonstrated that miR-34a is an important regulator in VSMC functions and neointima hyperplasia, suggesting its potential therapeutic application for vascular diseases. (c) 2015 Elsevier Ltd. All rights reserved.
