Xie Baodong, Zhang Chunfeng, Kang Kai, Jiang Shulin
Department of Cardiovascular Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
PLoS One. 2015 Nov 9;10(11):e0141512. doi: 10.1371/journal.pone.0141512. eCollection 2015.
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.
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。