Reasearch On Function And Mechanisms Of A Novel Small Molecule WG449E For Hypertrophic Scar

Hypertrophic scar is complication of severe wound healing.The dermis trauma,burns,surgery all result in the excessive repair in wound,which contributes to the formation of hypertrophic scar.Hypertrophic scar(HPS)is characterized by excessive fibrosis associated with aberrant function of fibroblasts.Hypertrophic scar not only brings financial burden to patients,but also accompany with a series of problems,including the destructive impact on patient’s appearance,the itch and pain feeling during scar proliferation period,the disfunction of tendon tissue.The most widely used method treating hypertrophic scar is combined therapy of surgery with steroid hormone injection.Although this method is effective to some extend,it can relieve the stress of scar,solve the uplift scar,it also has some side effects including skin atrophy,local skin necrosis,and there also existing a high recurrence rate.For this reason,it is of great significance to explore novel anti-HPS agents.In this study,we found a novel compound using the coll α2-luciferase reporter assay for the primary screening.The compound WG449E significantly down-regulated the mRNA and protein level of collagen in hypertrophic scar deprived fibroblasts through inhibiting smad2/3 phosphorylation.WG449E also inhibited the proliferation,migration and contraction of fibroblasts in vitro and in vivo.WG449E induced cell apoptosis through the activation of cleaved caspase3.Besides,WG449E treatment significantly attenuated hypertrophic scar formation and collagen deposition in a mechanical load-induced mouse model.To sum up,we discovered a novel small compound WG449E inhibiting hypertrophic scar,it showed excellent capacity of anti-scar in vitro and in vivo.WG449E can serve as a potential drug treating for hypertrophic scar,which providing valuable reference for drug development.