Metformin inhibits high glucose-induced smooth muscle cell proliferation and migration

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.

High glucose suppresses autophagy through the AMPK pathway while it induces autophagy via oxidative stress in chondrocytes

“…Notably, in vitro studies attempted to determine whether HG led to inhibition or activation of autophagy. HG resulted in decreased LC3II levels and elevated p62 levels in vascular smooth muscle cells 24 ; similarly, inhibition of HG-mediated autophagy was observed in the human neuroblastoma cell lines 25 . By contrast, Zhao et al established that excessive autophagy in H9c2 cells was induced in a HG medium 26 .…”

“…In OA, a converse outcome of defective autophagy was observed in diabetic patients with OA and experimental mice, suggesting that HG could compromise autophagy capacity in diabetic patients with OA 22 , 23 . The studies revealed contrasting results for in vivo experiments because the effects of DB on autophagy rather than HG could be attributed to several factors such as aging, inflammation, vascular injury, etc 24 , 25 . Notably, in vitro studies attempted to determine whether HG led to inhibition or activation of autophagy.…”

Metformin Inhibits the Phenotypic Transformation of Aortic Vascular Smooth Muscle Cells Induced by Hyperglycemia Through Regulation of the Mir-21-mediated PTEN/pAKT/Egr-1 Pathway

“…This study also found that metformin signi cantly reduced the migration ability of VSMCs induced by HG but had no signi cant effect on the proliferation of VSMCs. Dong M Zhou et al [37] also found similar results using metformin that inhibited HG-induced VSMC proliferation and migration by promoting the mir-142-3p mediated HMGB1 expression. The mechanism of metformin-mediated inhibition of migration still needs to be further studied.…”

Beyond Self-Recycling: Cell-Specific Role of Autophagy in Atherosclerosis

“…For example, telmisartan and irbesartan promote autophagy through the proliferator activated receptor-γ (PPARγ) and telmisartan attenuates lipid accumulation in VMSCs, which is rescued by Atg7 knockdown [ 191 , 192 ]. Finally, the widely used anti-diabetic drug metformin is an established inducer of endothelial cells and VSMCs autophagy and exerts anti-atherosclerotic features [ 193 , 194 , 195 , 196 ].…”