Int J Med Sci 2019; 16(7):960-966. doi:10.7150/ijms.32157

Research Paper

Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway

Rui Lei1, Shizhen Zhang2, Yuming Wang1, Siya Dai1, Jiaqi Sun1, Chaoqun Zhu3✉

1. Department of Plastic Surgery, The Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;
2. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
3. Department of Surgery, Family Planning Service Center Of YiWu Maternity And Child Health Care Hospital, Yiwu, China

Abstract

Background: Epithelial-to-mesenchymal transition (EMT) is a process whereby epithelial cells lose cell-cell contacts and acquire expression of mesenchymal components and manifest a migratory phenotype. Recent studies indicated that EMT is involved in the development of keloids. Therefore, this study aims to investigate the mechanisms of the effects of metformin in hypoxia-induced EMT in keloid fibroblasts (KFs).

Methods: KFs were cultured in a hypoxia incubator to induce EMT and were treated with or without metformin. Cell viability was evaluated by a cell counting kit 8 (CCK-8), and cell migration was measured by the transwell assay. The expression levels of HIF-1α, E-cadherin, vimentin, phosphorylated p70s6k (p-p70s6k) and pyruvate kinase M2 (PKM2) were evaluated by western blotting.

Results: Hypoxia promoted EMT in KFs. Metformin significantly inhibited the expression of HIF-1α and partially abolished hypoxia-induced EMT. PKM2 is involved in hypoxia-induced EMT of KFs and metformin decreased the expression of p-p70s6k and PKM2.

Conclusions: Metformin abolishes hypoxia-induced EMT in KFs by inhibiting the HIF-1α/PKM2 signaling pathway. Our study provides a novel mechanistic insight into potential use of metformin for treatment of keloids.

Keywords: Metformin, EMT, HIF-1α, PKM2, Keloid.

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How to cite this article:
Lei R, Zhang S, Wang Y, Dai S, Sun J, Zhu C. Metformin Inhibits Epithelial-to-Mesenchymal Transition of Keloid Fibroblasts via the HIF-1α/PKM2 Signaling Pathway. Int J Med Sci 2019; 16(7):960-966. doi:10.7150/ijms.32157. Available from http://www.medsci.org/v16p0960.htm