Amphibian-derived peptide RL-QN15 activates the Wnt/β-catenin signaling pathway by interacting with the FZD8 membrane receptor, promoting epidermal stem cells proliferation, migration, stemness, and EMT processes, thus promoting skin wound healing.
Abstract:
The pursuit of developing groundbreaking pro-regenerative therapies to expedite skin wound healing persists as a formidable challenge. Peptide RL-QN15, emerges as a highly promising candidate for the first pro-regenerative drug derived from amphibian skin, offering a glimmer of hope for innovative healing treatments. Yet, there is an urgent need for intensified research efforts to propel RL-QN15 from a molecular entity to a viable drug candidate, particularly in unraveling the mechanisms underlying its exceptional pro-healing efficacy. In the current research, our results revealed that RL-QN15 significantly enhanced the proliferation, migration, stemness, and epithelial-to-mesenchymal transition of human epidermal stem cells (hESCs) through direct binding to the membrane frizzled 8 (FZD8) receptor. This interaction triggers the downstream Wnt/β-catenin signaling pathway, leading to the up-regulation of target genes MYC and CCND1. Furthermore, RL-QN15 augmented the expression and secretion of matrix metalloproteinase-3, which degrades E-cadherin and activates the Wnt/β-catenin pathway, thereby amplifying RL-QN15’s regulatory effects on hESCs. In summary, our findings have demonstrated that RL-QN15 modulated the functions of ESCs to accelerate skin wound regeneration via the FZD8/β-catenin axis. This research not only advances peptide RL-QN15 from a molecular entity to a drug candidate by shedding light on the mechanisms involved with regulation of ESCs functions, but also presents compelling evidence implicating FZD8 as a novel therapeutic target for skin wound regeneration.
Author list:
Yuansheng Li†, Qiuye Jia†, Naixin Liu, Saige Yin, Junyuan Wang, Yujing Ding, Yuliu Yang, Ying Peng, Zeqiong Ru, Shaoyang Zhang, Bu’er Qi, Jun Sun, Li He*, Ying Wang*, Kun Guo*, Xinwang Yang*
How to cite:
Y. Li, Q. Jia, N. Liu, S. Yin, J. Wang, Y. Ding, Y. Yang, Y. Peng, Z. Ru, S. Zhang, B. Qi, J. Sun, L. He, Y. Wang, K. Guo, X. Yang, Exploration 2025, 20240090.
https://doi.org/10.1002/EXP.20240090