Peptide Cy_(RL-QN15)accelerates hair regeneration in diabetic mice by binding to the Frizzled-7 receptor

Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.