RL-QN15 Facilitates Vaginal Mucosal Repair by Coordinating Autophagy- Apoptosis Crosstalk

Abstract

Vaginal mucosa is a crucial protective barrier in the female reproductive tract, yet it remains susceptible to injury from infection, trauma, or estrogen deficiency, often leading to dysbiosis, chronic inflammation, and associated complications. Current therapies such as antibiotics and topical estrogen are limited by resistance and side effects, underscoring the need for new agents that restore mucosal integrity. Here, we assessed the regenerative potential of RL-QN15, an amphibian-derived pro-healing peptide, in vaginal mucosal repair. Using in vitro LPS-injured rat vaginal epithelial cells and an in vivo mucosal damage model, we found that RL-QN15 significantly promoted mucosal healing. Mechanistically, it suppressed inflammation via IL-6 downregulation, inhibited apoptosis by rebalancing Bax/Bcl-2 and reducing caspase-3 activation, and enhanced autophagy, as shown by an elevated LC3-II/LC3-I ratio and accelerated p62 degradation. Notably, RL-QN15 outperformed erythromycin in epithelial regeneration and tissue restructuring. Our study identifies RL-QN15 as a novel multi-target peptide that facilitates vaginal mucosal repair by coordinating autophagy-apoptosis crosstalk, highlighting its therapeutic potential for treating mucosal injury.