miR-145 inhibits the proliferation and migration of vascular smooth muscle cells by regulating autophagy.

miR-145, the most abundant miRNA in the vascular smooth muscle cells (VSMCs), regulates VSMC function in intimal hyperplasia. It has been reported that autophagy participates in the regulation of proliferation and migration of VSMCs. However, the effect of miR-145 on autophagy and related mechanism in the proliferation and migration of VSMCs remains unclear. Therefore, we aimed to determine the effect of miR-145 on autophagy and the mechanism in VSMCs. Cell autophagy was determined by transmission electron microscope, mRFP-GFP-LC3 assay and Western blotting. A recombinant lentivirus containing miR-145 was used to construct VSMCs with miR-145 overexpression. We found that miR-145 expression was decreased, and autophagy was increased in the carotid arteries of C57BL/6J mice with intimal hyperplasia and TGF-β1-stimulated VSMCs. Furthermore, miR-145 overexpression inhibited cell autophagy, whereas miR-145 inhibition promoted autophagy in TGF-β1-stimulated VSMCs. Meanwhile, miR-145 inhibited the proliferation and migration of VSMCs. More importantly, our study showed that autophagy inhibition augmented the inhibitory effect of miR-145 on the proliferation and migration of VSMCs. In addition, we found that the sirtuins are not direct targets of miR-145 in the proliferation and migration of VSMCs. These results suggest that miR-145 inhibits the proliferation and migration of VSMCs by suppressing the activation of autophagy. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Weirong Wang, Lifang Chen, Chenxu Shang, Zhen Jin, Feng Yao, Liang Bai, Rong Wang, Sihai Zhao, Enqi Liu. miR-145 inhibits the proliferation and migration of vascular smooth muscle cells by regulating autophagy. Journal of cellular and molecular medicine. 2020 Jun;24(12):6658-6669

Mesh Tags

Substances

PMID: 32337837

search → result