Peptide RL-QN15 derived from skin secretions of Rana limnocharis has a pronounced pro-healing effect on acute and chronic wounds, but its precise mechanism is remains to be elucidated. Epidermal stem cells are of utmost importance in wound healing and thus constitute a primary focus of wound repair research. Here, we explored the mechanism of RL-QN15 promoting wound healing by regulating epidermal stem cells. Our results showed that RL-QN15 activated the Wnt/β-catenin signaling pathway by binding to the FZD8. This interaction resulted in the up-regulation of target genes MYC and CCND1, thereby facilitating the proliferation of epidermal stem cells. MMP3 can degrade E-cadherin and activate Wnt/β-catenin pathway further. This enhanced pathway activity induced epithelial-to-mesenchymal transition and N-cadherin expression, further encouraging cell proliferation and migration. RL-QN15 can also effect the stemness of epidermal stem cells. In summary, as an excellent candidate for novel pro-healing agent, RL-QN15 can promote the activation of Wnt/β-catenin pathway through binding with membrane receptor FZD8, thus regulating epidermal stem cell functions and promoting wound healing. This study elucidated a novel mechanism by which amphibian-derived peptides promote skin wound healing, focusing on the regulatory role of epidermal stem cells and providing a new target for skin regeneration research.

Background and Purpose: Ischemia reperfusion (I/R) is the main cause of acute ischemic stroke injury. However, existing treatments for I/R injury are relatively poor, and relevant drugs need to be further explored. Experimental Approach: In this study, the neuroprotective function and related mechanism of OL-FS13 were studied through rat I/R model and PC12 cell model of oxygen glucose deprivation/reoxygenation model (OGD/R), combined with cell viability experiment, tissue H&E and Nissl staining experiment and Western blot experiment. Key Results: In this study, we identified a novel neuroprotective peptide (OL-FS13, amino acid sequence: FSLLLTWWRRRVC) from the odorous frog species Odorrana livida using a constructed cDNA library. OL-FS13 significantly alleviated brain injury from cerebral I/R in rats by reducing infarct volume in the brain, improving behavioral and histological abnormalities, and rescuing PC12 cell from damage caused by oxygen glucose deprivation/reoxygenation (OGD/R). Mechanistically, OL-FS13 increased the level of antioxidative enzymes to resist oxidative stress induced by I/R and OGD/R by activating the Nrf2/HO-1 pathway and alleviated endoplasmic reticulum (ER) stress induced by OGD/R by inhibiting the IRE1α/TRAF2/JNK pathway. Conclusion and Implications: Collectively, the novel peptide exerted significant anti-stroke activities by alleviating oxidative and ER stress via activation of Nrf2 signaling and suppression of the IRE1α/TRAF2/JNK pathway. Thus, this research provides a potential drug candidate for the clinical treatment of cerebral I/R.

At present, there are no satisfactory therapeutic drugs for the functional recovery of spinal cord injury (SCI). We previously identified a novel peptide (OM-LV20) that accelerated the regeneration of injured skin tissues of mice and exerts neuroprotective effects against cerebral ischemia/reperfusion injury in rats . Here, the intraperitoneal injection of OM-LV20 (1 μg/kg) markedly improved motor function recovery in the hind limbs of rats with traumatic SCI, and further enhanced spinal cord repair. Administration of OM-LV20 increased the number of surviving neuron bodies, as well as the expression levels of brain-derived neurotrophic factor and its receptor tyrosine receptor kinase B. In the acute stage of SCI, OM-LV20 treatment also increased superoxide dismutase and glutathione content but decreased the levels of malonaldehyde and nitric oxide. Thus, OM-LV20 significantly promoted structural and functional recovery of SCI in adult rats by increasing neuronal survival and BDNF and TrkB expression, and thereby regulating the balance of oxidative stress. Based on our knowledge, this research is the first report on the effects of amphibian-derived peptide on the recovery of SCI and our results highlight the potential of peptide OM-LV20 administration in the acceleration of the recovery of SCI.