The Pro-Healing Effect of Protamine-Hydrolysate Peptides on Skin Wounds Involves TGF-β/Smad Signaling

This study characterized the molecular mechanisms of the effects of protamine-hydrolysate peptides (p-h peptides) on skin wound healing in rats by analyzing the transforming growth factor (TGF)-β signaling pathway. TGF-β was expressed in experimentally wounded skin tissues in fibroblasts and in keratinocytes. In p-h peptides-treated animals, the skin wounds exhibited an increased expression of TGF-β and of TGF-β target genes compared with control saline-treated skin wounds. Treatment with p-h peptides accelerated wound epithelialization and induced protein expression of TGF-β, CTGF and VEGF. The expression of tumor necrosis factor (TNF)-α was decreased in fibroblasts of p-h peptides-treated skin wounds. In addition, treatment with p-h peptides significantly enhanced the phosphorylation of Smad3 and Smad4 in fibroblasts and also elevated the phosphorylation of Stat3 in skin wound tissues. In conclusion, treatment with p-h peptides activated the Smad-dependent TGF-β signaling pathway, enhanced the differentiation of myofibroblasts and accelerated skin wound closure.