Hypertrophic scar(HS)is a serious skin fibrotic disease characterized by excessive hypercellularity and extracellular matrix(ECM)component deposition.Autophagy is a tightly regulated physiological process essential for cellular maintenance,differentiation,development,and homeostasis.However,in the formation of HS,the autophagy in dermal fibroblasts is poorly understood.Here we compared the autophagy in HS and normal skin(NS)counterparts by immunohistochemistry and transmission electron microscopy(TEM),explored and verified the regulation key molecular of autophagy using HS-derived fibroblasts(HSFs),and validated by rabbit ear scar model.The data showed that LC3 positive staining and autophagosomes in HS was more intensive relative to NS group(p < 0.05).Knockdown for LC3(shLC3)blocks the expression of Col 1(p < 0.05)and Col 3(p < 0.05)to inhibit the fibrosis of HS-derived fibroblasts(HSFs),and shLC3 resistant to autophagy was shown to be dependent on Bcl-xL inactivation,not independent on Bcl-2.And silence Bcl-xL(siBcl-xL)significantly increase HSFs apoptosis(p < 0.05).Interestingly,Immunofluorescence analysis showed shLC3 significantly inhibited the expression of α-SMA mainly through destroying its synthetic and arrangement.Knockdown of Bcl-xL(siBcl-xL)show that Bcl-xL is a key and signaling molecule involved in autophagy in HSFs.More important,in the rabbit ear scar model,both shLC3 and siBcl-xL significantly improved the architecture and reduced scar formation on the rabbit ear.Our results suggest that the resultant increase of autophagic capacity associate with the pathogenesis of HS,and indicate that LC3 mediate the expression of Col 1 and Col 3 and scarring of the rabbit ear by the targets molecular Bcl-xL to regulate HS formation and its fibrosis.Therefore,Bcl-xL could serve as a potential molecular target,and might be a novel strategy for HS therapy.