Mast cell chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating TGF-beta 1/Smads signaling pathway

摘要

The present study assessed the existence of mast cell chymase in hypertrophic scars and determined whether chymase promotes fibrosis via the transforming growth factor (TGF)-beta 1/Smads signaling pathway. Five patients with hypertrophic scars and another five patients subjected to repair and reconstruction of other tissue defects were included in the present study. To detect the existence of mast cells and mast cell chymase in hypertrophic scars, immunohistochemistry was employed. To test the effect of chymase on TGF-beta 1, angiotensin, and type I and III collagen mRNA expression in isolated hypertrophic scar fibroblasts in vitro, reverse-transcription quantitative PCR was performed. To investigate how chymase affects TGF-beta 1, phosphorylated (P)-Smad2/3 as well as Smad4 and Smad7 protein expression, western blot analysis was used. Mast cell chymase was identified to promote the mRNA expression of TGF-beta 1, angiotensin, and type I and III collagen in hypertrophic scar fibroblasts in a time-and dose-dependent manner. Furthermore, treatment with 60 ng/ml mast cell chymase for 12 h led to the upregulation of TGF-beta 1, P-Smad2/3, Smad4 and Smad7 in hypertrophic scar fibroblasts. The present study demonstrated that mast cells and chymase are present in hypertrophic scars, and chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating the TGF-beta 1/Smads signaling pathway.