Linagliptin inhibits high glucose‐induced transdifferentiation of hypertrophic scar‐derived fibroblasts to myofibroblasts via IGF/Akt/mTOR signalling pathway

Hypertrophic scar (HS) is a fibroproliferative disease after serious burns; the underlying mechanism remains unknown. The study was performed to clarify the effect of high glucose (HG) on HS. The expression of Col1, Col3 and α‐SMA was upregulated in HS‐derived fibroblasts (HSF) exposed to HG (20 and 30 mmol/L), and HG activated the phosphorylated protein expression of IGF/Akt/mTOR signalling pathway in HSF. Dpp4, a marker targeted the treatment of diabetes mellitus, was overexpressed in HG‐induced HSF. Linagliptin, a Dpp4 inhibitor, played the antifibrotic role in HSF exposed to HG, the levels of Col1, Col3 and α‐SMA were significantly downregulated, and the cell proliferation and migration were also inhibited. Furthermore, linagliptin alleviated the phosphorylated protein expression of IGF/Akt/mTOR signalling pathway. Moreover, the mTOR inhibitor (rapamycin) mimicked the effect of linagliptin on the collagen and α‐SMA that means linagliptin may inhibit HG‐induced transdifferentiation of HSF to myofibroblasts via IGF/Akt/mTOR signalling pathway.