Pirfenidone ameliorates hypertrophic scar through inhibiting proliferation and migration of fibroblasts by regulating the Wnt/GSK-3β/β-catenin signaling pathway.

Abstract

Hypertrophic scar (HS) is a prevalent complication that arises from burn injuries. While Pirfenidone (PFD) is known to be an effective antifibrotic agent, its precise effects on HS caused by burn injuries are still unclear. This study was to assess the influence of PFD on HS fibroblasts and investigate the underlying mechanism. HS tissue and normal skin tissue samples were collected, and fibroblasts were isolated from HS tissues and normal skin. The cytotoxic effect was detected by lactate dehydrogenase (LDH). Cell proliferation was detected by CCK-8 and EdU methods, and migration was detected by Transwell. Transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), and type I collagen (COL-I) mRNA expression levels were analyzed by RT-qPCR. TGF-β1, α-SMA, COL-I, and APC protein expression levels, as well as phosphorylation of GSK-3β and β-catenin were detected by Western blot. The results indicated that PFD inhibited the proliferation of HS fibroblasts without cytotoxicity. PFD inhibited the migration of HS fibroblasts and differentiation by inhibiting TGF-β1, α-SMA, and Col-I expression. PFD reduced the phosphorylation of GSK-3β and β-catenin, suppressed APC protein expression, and blocked the Wnt/GSK-3β/β-catenin cascade. PFD can ameliorate HS after burn injuries and inhibit proliferation and differentiation of HS fibroblasts through the Wnt/GSK-3β/β-catenin cascade.