Peptide RL-QN15 regulates epidermal stem cell function to accelerate wound healing via the FZD8/β-catenin axis

Peptide RL-QN15 derived from skin secretions of Rana limnocharis has a pronounced pro-healing effect on acute and chronic wounds, but its precise mechanism is remains to be elucidated. Epidermal stem cells are of utmost importance in wound healing and thus constitute a primary focus of wound repair research. Here, we explored the mechanism of RL-QN15 promoting wound healing by regulating epidermal stem cells. Our results showed that RL-QN15 activated the Wnt/β-catenin signaling pathway by binding to the FZD8. This interaction resulted in the up-regulation of target genes MYC and CCND1, thereby facilitating the proliferation of epidermal stem cells. MMP3 can degrade E-cadherin and activate Wnt/β-catenin pathway further. This enhanced pathway activity induced epithelial-to-mesenchymal transition and N-cadherin expression, further encouraging cell proliferation and migration. RL-QN15 can also effect the stemness of epidermal stem cells. In summary, as an excellent candidate for novel pro-healing agent, RL-QN15 can promote the activation of Wnt/β-catenin pathway through binding with membrane receptor FZD8, thus regulating epidermal stem cell functions and promoting wound healing. This study elucidated a novel mechanism by which amphibian-derived peptides promote skin wound healing, focusing on the regulatory role of epidermal stem cells and providing a new target for skin regeneration research.