Objective: To investigate the mechanism of metformin(MET) on hypoxia-induced keloid fibroblasts(KFs) epithelial-mesenchymal transition(EMT). Methods: KFs was divided into a hypoxic group and a control group. KFs in the hypoxic group were cultured in a hypoxic environment to induce EMT, while KFs in the control group were normal cultured. Additionally, KFs were treated with fibroblast growth factor receptor 4(FGFR4) overexpression vector(FGFR4-OE) or empty vector(EV) in the presence of MET and under hypoxic conditions, respectively. KFs were treated with recombinant human macrophage stimulation 1(rhMST1) protein in the presence of MET and hypoxia. KFs under hypoxia were divided into saline group, MET group, EV+MET group, FGFR4-OE+MET group and rhMST1+MET group. Cell proliferation viability was assessed by cell counting kit 8(CCK-8), and cell migration was measured by migration chamber assay. Expression levels of FGFR4, E-cadherin, vimentin and MST1 were assessed by western blotting. Results: Compared with the control group, the cell proliferation activity of KFs, migration rate and EMT in the hypoxia group were significantly increased. The expressions of FGFR4 and MST1, as well as hypoxia-induced cell proliferation activity, migration rate and EMT markers in the MET group were significantly lower than those in the normal saline group(P<0.05). Compared with the MET group and the EV+MET group, the expressions of FGFR4 and MST1, as well as the hypoxia-induced cell proliferation activity, migration rate and EMT markers in the FGFR4-OE+MET group were significantly increased(P<0.05). Compared with the MET group, the MST1 expression and hypoxia-induced cell proliferation activity, migration rate and EMT markers in the rhMST1+MET group were significantly increased(P<0.05). Conclusion: MET abrogates hypoxia-induced EMT in KFs by inhibiting the FGFR4/MST1 signaling pathway. |
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