Anti-fibrotic effects of evogliptin in fibroblasts derived from post-burn hypertrophic scars

Hypertrophic scar (HTS) frequently occurs after burn injury, characterized by persistent fibroblast activation, overexpression of α-smooth muscle actin (αSMA) and extracellular matrix (ECM) components. Complete scarless regeneration remains incompletely understood. Dipeptidyl peptidase-4 (DPP4) is a cell-surface serine protease, its inhibitors (DPP4i) have been associated with fibrosis. However, the functional role of evogliptin in HTS formation remains unclear. This investigated its effects on fibrosis markers in hypertrophic scar fibroblasts (HTSFs). Human normal fibroblasts (HNFs) and HTSFs were isolated from normal skin and post-burn HTS tissues. DPP4 expression in HTS and normal skin tissues was detected using immunocytochemistry. mRNA and protein expression levels were determined via quantitative real-time polymerase chain reaction and western blot, respectively. Evogliptin treatment in HTSFs and HNFs treated with transforming growth factor-beta 1 (TGF-β) both inhibited the expression of differentiation markers, including αSMA, TGF-β1, YAP1, TEAD1, and CTGF, thereby reducing fibroblast activation; ECM components, including type Ⅰ collagen, type Ⅲ collagen, and fibronectin; epithelial-mesenchymal transition (EMT) markers, including snail1, slug, twist1, vimentin, and n-cadherin; and TGF-β-mediated signaling molecules, including SMAD2, SMAD3, TAK1, ERK, p38, JNK, AKT, and STAT3. Our results demonstrated that evogliptin exerts its anti-fibrotic activity by inhibiting fibroblast activation, EMT, and ECM synthesis in HTSFs.