Peptide Cy<sub>RL-QN15</sub> accelerates hair regeneration in diabetic mice by binding to the Frizzled-7 receptor
Yutong Wu, Zeqiong Ru, Ru Ze-Qiong, Peng Ying, Fu Zhe, Jia Qiu-Ye, Kang Zi-Jian, Li Yuan-Sheng, Huang Yu-Bing, Yin Sai-Ge, Guo Kun, Liu Nai-Xin, Feng Cheng-An, Tang Jing, Zhang Bai-Yu, Yang Zhi, Wang Ying, Yang Xin-Wang, 云南民族大学民族医学院民族药用资源化学重点实验室和民族药用内生植物天然产物合成生物学重点实验室, 云南 昆明 650504, 中国, 昆明医科大学基础医学院医学生物化学与分子生物学系, 云南 昆明650500, 中国, 昆明医科大学附属第一医院泌尿科, 云南 昆明 650500, 中国, 昆明医科大学附属第一医院皮肤科, 云南 昆明 650500, 中国, 昆明医科大学云南省天然产物药理学重点实验室, 云南 昆明 650500, 中国
Abstract
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<sub>RL-QN15</sub>, on promoting hair regeneration in a diabetic skin model. <italic>In vivo</italic> experiments demonstrated that local treatment with Cy<sub>RL-QN15</sub> 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<sub>RL-QN15</sub> treatment. Further analysis indicated that the hair-regenerating effects of Cy<sub>RL-QN15</sub> were closely associated with the proliferation and migration of hair follicle stem cells (HFSCs). Cy<sub>RL-QN15</sub> 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<sub>RL-QN15</sub> 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.