Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Exp Dermatol. 2019 Jan;28(1):19-27. doi: 10.1111/exd.13800. Epub 2018 Dec 5.
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.
增生性瘢痕（HS）是严重烧伤后的一种纤维增生性疾病；其潜在机制尚不清楚。本研究旨在阐明高葡萄糖（HG）对 HS 的影响。在高葡萄糖（20 和 30mmol/L）作用下，HS 来源的成纤维细胞（HSF）中 Col1、Col3 和 α-SMA 的表达上调，HG 激活了 HSF 中 IGF/Akt/mTOR 信号通路的磷酸化蛋白表达。Dpp4 是一种针对糖尿病治疗的标志物，在 HG 诱导的 HSF 中过度表达。Dpp4 抑制剂 linagliptin 在高葡萄糖作用下的 HSF 中发挥抗纤维化作用，Col1、Col3 和 α-SMA 的水平显著下调，细胞增殖和迁移也受到抑制。此外，linagliptin 减轻了 IGF/Akt/mTOR 信号通路的磷酸化蛋白表达。此外，mTOR 抑制剂（雷帕霉素）模拟了 linagliptin 对胶原和 α-SMA 的作用，这意味着 linagliptin 可能通过 IGF/Akt/mTOR 信号通路抑制 HG 诱导的 HSF 向肌成纤维细胞的转分化。
