Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Biomed Pharmacother. 2018 Mar;99:81-86. doi: 10.1016/j.biopha.2018.01.014. Epub 2018 Jan 8.
The excessive proliferation and migration of vascular smooth muscle cells (VSMCs) are important steps in atherosclerosis. The present study aimed to investigate whether the high glucose-induced changes of VSCMs are mediated by miR-145 and the potential molecular mechanism involved. We found that loss of miR-145 accompanied with increased proliferation and migration was observed in cultured human VSMCs exposed to high glucose. Exogenous overexpression of miR-145 effectively suppressed the high glucose-induced excessive proliferation and migration of VSMCs. Furthermore, we identified ROCK1 as a downstream target gene product of miR-145, and ROCK1 partially rescues the effects of miR-145 on high glucose-induced VSMC proliferation and migration. Taken together, our results suggested a protective role of miR-145 in high glucose-treated VSMCs by suppressing ROCK1, which might provide a therapeutic target for diabetic atherosclerosis.
血管平滑肌细胞(VSMCs)的过度增殖和迁移是动脉粥样硬化的重要步骤。本研究旨在探讨高糖是否通过 miR-145 介导的变化来影响 VSCMs,以及涉及的潜在分子机制。我们发现,在暴露于高葡萄糖的培养的人 VSMCs 中,miR-145 的缺失伴随着增殖和迁移的增加。外源性过表达 miR-145 可有效抑制高葡萄糖诱导的 VSMCs 的过度增殖和迁移。此外,我们鉴定出 ROCK1 是 miR-145 的下游靶基因产物,ROCK1 部分挽救了 miR-145 对高葡萄糖诱导的 VSMC 增殖和迁移的作用。总之,我们的研究结果表明,miR-145 通过抑制 ROCK1 在高糖处理的 VSMCs 中发挥保护作用,这可能为糖尿病性动脉粥样硬化提供治疗靶点。