研究领域：药理学 生物化学 分子生物学 伤口愈合

关键字：新型短肽 伤口愈合 RL-QN15 泽蛙 MAPK Smad信号通路 细胞因子 巨噬细胞 皮肤细胞 TGF-β1 TGF-β3 再上皮化 肉芽组织 慢性伤口 皮肤纤维化 口腔溃疡

尽管已投入大量努力开发有效的治疗策略，皮肤伤口的治疗仍是当前临床面临的重要挑战。现有疗法尚无法充分满足临床需求，因此发现新型促愈合剂日益重要。本研究从沼蛙（Rana limnocharis）皮肤分泌物中鉴定出一种新型短肽（命名为RL-QN15，一级序列为‘QNSYADLWCQFHYMC’），该肽可显著加速小鼠皮肤伤口愈合。机制研究表明，RL-QN15可激活MAPK和Smad信号通路，并选择性调控巨噬细胞的细胞因子分泌，从而促进皮肤细胞增殖与迁移，并动态调节伤口局部转化生长因子-β1（TGF-β1）和转化生长因子-β3（TGF-β3）的表达，进而加速再上皮化与肉芽组织形成，最终促进皮肤再生。此外，RL-QN15对慢性伤口、皮肤纤维化及口腔溃疡亦展现出显著治疗潜力。本研究结果提示，蛙类皮肤分泌物是具有促愈活性生物活性肽的潜在宝库；本研究所鉴定的新型肽RL-QN15具备作为新型促愈合剂候选分子的重要开发价值。Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence ‘QNSYADLWCQFHYMC’) from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-β1 and TGF-β3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis , and oral ulcers . Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.