Cy RL-QN15

The skin, a vital barrier against environmental damage, plays a crucial role in maintaining organismal homeostasis. However, the molecular mechanisms underlying skin wound repair remain incompletely understood, with microRNA regulation potentially serving as a key regulatory component. Utilizing the amphibian-derived cyclic peptide Cy_RL-QN15 as a molecular probe, we identified the miR-181d-5p/Ikbkg/NF-κB axis as significantly associated with wound healing through small RNA sequencing of early-stage skin injury. Mechanistically, inhibition of miR-181d-5p during the early phase elevated the release of pro-inflammatory cytokines (TNF-α, IL-1β) and enhanced macrophage migration. In vivo, inhibition of miR-181d-5p accelerated full-thickness skin wound healing in mice, confirming its role in promoting the inflammatory phase transition. Collectively, these findings indicate that early suppression of miR-181d-5p activates the Ikbkg/NF-κB signaling pathway, thereby facilitating the transition from the inflammatory to the proliferative phase and accelerating skin repair. Conducted within the regulatory network of ceRNA, the study uncovers the potential of miR-181d-5p as a therapeutic target for wound healing and provides a novel interventional strategy for enhancing skin repair.

Skin photoaging, a process with substantial physical and psychological impacts, is also a recognized risk factor for skin cancer. Despite advancements in dermatological research, effective prevention and reversal of photoaging remain challenging. This study investigated the efficacy of Cy_RL-QN15, an optimized variant derived from the RL-QN15 peptide, in mitigating ultraviolet B (UVB)-induced skin photoaging in mice. Results showed that Cy_RL-QN15 promoted skin barrier repair and exhibited antioxidant and anti-apoptotic properties. Mechanistically, these effects were mediated by activating the downstream Wnt/β-catenin signaling pathway. Notably, the therapeutic efficacy of Cy_RL-QN15 was diminished by using the inhibitor MSAB, suggesting a crucial role for the β-catenin signaling pathway. Furthermore, Cy_RL-QN15 may exert its effects by binding to the Frizzled-8 receptor on the human keratinocyte (HaCaT) cell membranes. This study is the first to identify the role of β-catenin regulation in skin barrier dysfunction during photoaging, establishing a potential therapeutic foundation for targeting Cy_RL-QN15 to combat skin photoaging.