Research Paper Volume 12, Issue 6 pp 5352—5361
Metformin inhibits high glucose-induced smooth muscle cell proliferation and migration
- 1 Department of Hematology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
- 2 Department of Vascular Surgery, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
- 3 Department of Vascular Surgery, The Second Affiliated Hospital of Soochow University, Jiangsu, China
- 4 Department of Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, China
Received: December 30, 2019 Accepted: February 20, 2020 Published: March 24, 2020
https://doi.org/10.18632/aging.102955How to Cite
Copyright © 2020 Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
We investigated the protective effects and mechanism of action of metformin on high glucose-induced smooth muscle cell proliferation and migration. Vascular smooth muscle cells (VSMCs) were subjected to a series of concentrations (0-10 mM) of metformin. CCK-8, wound healing, and transwell assays were performed. Correlations between metformin concentration and high-mobility group box 1 (HMGB1) and miR-142-3p levels were assessed. In addition, miR-142-3p mimic and siRNA were used to investigate VSMC migration in the presence or absence of metformin. In the high-glucose condition, metformin decreased cell growth and inhibited cell migration. HMGB1 gene expression correlated negatively with metformin concentration, whereas miR-142-3p expression correlated positively with metformin concentration. In addition, mimic-induced miR-142-3p elevation resulted in decreased HMGB1 and LC3II levels and elevated p62 levels in the high-glucose condition, whereas miR-142-3p knockdown had the reverse effects, and metformin abolished those effects. Metformin inhibits high glucose–induced VSMC hyperproliferation and increased migration by inducing miR-142-3p-mediated inhibition of HMGB1 expression via the HMGB1-autophagy related pathway.