Forkhead-box C1 attenuates high glucose-induced trophoblast cell injury during gestational diabetes mellitus via activating adenosine monophosphate-activated protein kinase through regulating fibroblast growth factor 19.

Gestational diabetes mellitus (GDM) is a complication developed during pregnancy and recover after childbirth. The purpose of this study was to investigate the protective role of FOXC1 during GDM and the underlying mechanism. FOXC1 was downregulated in GDM placental tissues and HG-treated HTR-8/SVneo cells. Overexpression of FOXC1 prevented HG-induced inhibition of cell proliferation, migration and invasion. FOXC1 suppressed HG-induced cell apoptosis in HTR-8/SVneo cells. The apoptosis-related proteins: cleaved caspase-3, cleaved caspase-9 and BAX, were also downregulated by FOXC1 overexpression. FOXC1 increased glucose uptake and improved insulin sensitivity. The expression of FOXC1 was positively correlated with FGF19 expression. FOXC1 regulated the expression of FGF19 and phosphorylation of AMPK. Inhibition of FGF19 attenuated the biological functions of FOXC1 through inactivation of AMPK. In conclusion, this study demonstrates that FOXC1 attenuates HG-induced trophoblast cell injury through upregulating FGF19 to activate the AMPK signaling pathway during GDM, suggesting that FOXC1 is a potential therapeutic target for drug discovery in the future.