• Rui Lei, Shizhen Zhang, Yuming Wang, Siya Dai, Jiaqi Sun, and Chaoqun Zhu.
• Department of Plastic Surgery, The Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
• Int J Med Sci. 2019 Jan 1; 16 (7): 960966960-966.

AbstractBackground: 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.

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