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微小RNA-599通过靶向转化生长因子β2抑制血管平滑肌细胞增殖和迁移。

miR-599 Inhibits Vascular Smooth Muscle Cells Proliferation and Migration by Targeting TGFB2.

作者信息

Xie Baodong, Zhang Chunfeng, Kang Kai, Jiang Shulin

机构信息

Department of Cardiovascular Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

PLoS One. 2015 Nov 9;10(11):e0141512. doi: 10.1371/journal.pone.0141512. eCollection 2015.

Abstract

Aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of cardiovascular diseases including coronary heart disease, restenosis and atherosclerosis. MicroRNAs are a class of small, non-coding and endogenous RNAs that play critical roles in VSMCs function. In this study, we showed that PDGF-bb, as a stimulant, promoted VSMCs proliferation and suppressed the expression of miR-599. Moreover, overexpression of miR-599 inhibited VSMCs proliferation and also suppressed the PCNA and ki-67 expression. In addition, we demonstrated that ectopic expression of miR-599 repressed the VSMCs migration. We also showed that miR-599 inhibited type I collagen, type V collagen and proteoglycan expression. Furthermore, we identified TGFb2 as a direct target gene of miR-599 in VSMCs. Overexpression of TGFb2 reversed miR-599-induced inhibition of VSMCs proliferation and type I collagen, type V collagen and proteoglycan expression. In conclusion, our findings suggest miR-599 plays a crucial role in controlling VSMCs proliferation and matrix gene expression by regulating TGFb2 expression.

摘要

血管平滑肌细胞(VSMCs)的异常增殖和迁移在包括冠心病、再狭窄和动脉粥样硬化在内的心血管疾病发病机制中起关键作用。微小RNA是一类小的、非编码的内源性RNA,在VSMCs功能中起关键作用。在本研究中,我们表明,作为一种刺激物,血小板源性生长因子BB(PDGF-bb)促进VSMCs增殖并抑制miR-599的表达。此外,miR-599的过表达抑制VSMCs增殖,并抑制增殖细胞核抗原(PCNA)和ki-67的表达。此外,我们证明miR-599的异位表达抑制VSMCs迁移。我们还表明,miR-599抑制I型胶原、V型胶原和蛋白聚糖的表达。此外,我们确定转化生长因子β2(TGFb2)是VSMCs中miR-599的直接靶基因。TGFb2的过表达逆转了miR-599诱导的VSMCs增殖抑制以及I型胶原、V型胶原和蛋白聚糖的表达。总之,我们的研究结果表明,miR-599通过调节TGFb2表达在控制VSMCs增殖和基质基因表达中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28dd/4638351/bc52181d8292/pone.0141512.g001.jpg

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