Abstract
Abstract in English, Chinese 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 hair-regenerating effects of Cy RL-QN15 were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy RL-QN15 enhanced intracellular β-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs. The up-regulation in β-catenin modulated the levels of downstream proteins, such as c-MYC, 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. 糖尿病是一种常见的疾病，患者常常面临伤口愈合延迟和感染风险增加等严峻挑战。毛囊的再生对于加速糖尿病皮肤损伤修复、降低感染风险和提升皮肤整体健康具有重要的作用。然而，目前相关的研究还存在不足。该研究旨在探究一种源自两栖动物的生物活性肽Cy RL-QN15在促进糖尿病皮肤毛发生长方面的作用。体内实验表明，局部使用Cy RL-QN15不仅加速了糖尿病昆明小鼠背部烫伤皮肤的伤口愈合，还改善了受损毛囊的生长。此外，对经过连续28天Cy RL-QN15治疗的糖尿病C57BL/6小鼠背部新生毛发进行分析，结果显示其数量显著增加。进一步研究发现，Cy RL-QN15的促毛发生长作用与毛囊干细胞的增殖和迁移密切相关。Cy RL-QN15通过与毛囊干细胞表面的Frizzled-7受体结合，增强了细胞内β-连环蛋白的表达。上调的β-连环蛋白进一步调节了其下游相关蛋白（如c-MYC、Cyclin D1和Lef1）的水平，并最终诱导毛发生长。该研究不仅揭示了生物活性肽Cy RL-QN15对毛发再生的显著促进作用，还为未来开发更具针对性和有效的糖尿病伤口高质量愈合药物提供了新的方案。.