The pro-healing effect of protamine-hydrolysate peptides on skin wounds involves TGF-β/smad signaling

Abstract

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 ph 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 Smaddependent TGF-β signaling pathway, enhanced the differentiation of myofibroblasts and accelerated skin wound closure.