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微小 RNA-145 通过靶向 ROCK1 减轻高糖诱导的血管平滑肌细胞增殖和迁移。

MicroRNA-145 alleviates high glucose-induced proliferation and migration of vascular smooth muscle cells through targeting ROCK1.

机构信息

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.

出版信息

Biomed Pharmacother. 2018 Mar;99:81-86. doi: 10.1016/j.biopha.2018.01.014. Epub 2018 Jan 8.

Abstract

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.

摘要

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。

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