Cheong Hoon Seo, Hui Song Cui, June-Bum Kim
Introduction: Hypertrophic scars represent the most common complication resulting from burn injury, and their pathological hallmark is excessive deposition of fibroblast-derived extracellular matrix proteins. Calpain, a calcium-dependent endopeptidase, mediates fibroblast activation and collagen synthesis, leading to the development of certain fibrotic diseases; however, its role in hypertrophic skin scar formation following a burn injury remains unclear. Objective: This study aimed to investigate the role of calpain and anti-fibrotic potential of PD150606, a calpain inhibitor, in post-burn hypertrophic scar formation. Methods: A detailed evaluation of the expression and activity of calpain in skin fibroblasts obtained directly from patients with third-degree burns, who subsequently developed post-burn hypertrophic scars, was performed. The antifibrotic effect of targeted inhibition of calpain by PD150606 on post-burn skin scarring was evaluated in vitro and in vivo. Results: The mRNA and protein expression and activity of calpain were significantly higher in burn wound fibroblasts from patients than in normal cells. Selective inhibition of calpain by PD150606 significantly reduced the proliferation of burn wound fibroblasts as well as the mRNA and protein expression of calpain and hypertrophic markers in these cells. Furthermore, the molecular, histological, and visual effects related to post-burn scar suppression by PD150606 were verified in murine burn models. Conclusions: The results obtained herein highlight the pathophysiological role of calpain and indicate that calpain inhibition by PD150606 could serve as a new therapeutic strategy for preventing hypertrophic scar formation following burn injury.