Key Laboratory of Chemistry in Ethnic Medicine Resource, State Ethnic Affairs Commission & Ministry of Education, School of Ethno-Medicine and Ethno-Pharmacy, Yunnan Minzu University, Kunming, Yunnan, 650504, China.
Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, China.
Pharmacol Res. 2021 Jan;163:105296. doi: 10.1016/j.phrs.2020.105296. Epub 2020 Nov 19.
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.
尽管人们已经做出了广泛的努力来开发有效的治疗方法，但皮肤伤口的治疗仍然是一个重大的临床挑战。现有的治疗方法不能充分满足当前的需求，因此发现新的促愈剂变得越来越重要。在当前的研究中，我们从中华大蟾蜍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'），它能加速小鼠的伤口愈合。对潜在机制的探索表明，RL-QN15 激活了 MAPK 和 Smad 信号通路，并选择性地调节了巨噬细胞细胞因子的分泌。这导致皮肤细胞的增殖和迁移，以及 TGF-β1 和 TGF-β3 在伤口中的动态调节，从而加速了上皮再形成和肉芽组织的形成，进而促进了皮肤再生。此外，RL-QN15 对慢性伤口、皮肤纤维化和口腔溃疡均显示出显著的治疗效果。我们的研究结果强调了青蛙皮肤分泌物是具有愈合活性的生物活性肽的潜在宝库。本研究中鉴定出的新型肽（RL-QN15）具有作为新型促愈剂候选物的巨大潜力。
