OM-LV20, a novel peptide from odorous frog skin, accelerates wound healing in vitro and in vivo
| 期刊:Chemical Biology & Drug Design | 发表时间: 2017-06-26 | 影响因子: 2.396 | ||
| 作者列表:JXiaojie Li, Ying Wang, Zhirong Zou, Meifeng Yang, Chunyun Wu, Yunshan Su, Jing Tang, Xinwang Yang | ||||
| 第一作者国家: 中国 | 第一作者单位: 昆明医科大学 | |||
| 通讯作者国家: 中国 | 通讯作者单位: 昆明医科大学 | |||
研究领域:生物化学 药理学 分子生物学
关键字:OM-LV20 伤口愈合 生物活性肽 人类角质细胞 小鼠模型
慢性伤口的愈合在临床实践中仍面临重大挑战,并给患者带来严重的经济负担和生理负担。目前,研究者正致力于开发理想的促进伤口愈合的临床用生物材料。具有成本低廉、易于生产、储存与运输等优势的小分子生物活性肽成为极具前景的候选物。本研究从臭蛙(Odorrana margaretae)皮肤分泌物中鉴定出一种新型肽(命名为OM-LV20),其氨基酸序列为“LVGKLLKGAVGDVCGLLPIC”,C末端含有分子内二硫键,由含71个氨基酸残基的前前体肽经翻译后加工产生。实验结果表明,OM-LV20不具有直接的抗菌活性、溶血活性或急性毒性,仅表现出微弱的抗氧化活性;但其可呈时间依赖性和剂量依赖性地促进人角质形成细胞(HaCaT)和人皮肤成纤维细胞(HSF)的伤口愈合;此外,OM-LV20可诱导HaCaT细胞增殖,但对HSF细胞无此作用。值得注意的是,OM-LV20在小鼠全层皮肤缺损模型中展现出显著的促伤口愈合活性。本研究证实了OM-LV20在细胞及动物水平上的促伤口愈合潜力,为其作为新型生物活性肽模板用于伤口愈合药物的研发提供了理论依据与实践基础。The healing of chronic wounds remains a considerable challenge in clinical trials and imposes severe financial and physiological burdens on patients. Many works are being tried to find ideal clinical promoting wound healing biomaterials. Small bioactive peptides with low cost and easy production, store and transfer become excellent candidates. Here, we identified a novel peptide (named OM-LV20) from skin secretions of odorous frog Odorrana margaretae . The peptide had an amino acid sequence of “LVGKLLKGAVGDVCGLLPIC,” contained an intramolecular disulfide bridge at the C-terminus, and was produced by post-translational processing of a 71-residue prepropeptide. Our results showed that OM-LV20 had no direct microbe-killing effects, hemolytic activity, or acute toxicity, but did exhibit weak antioxidant activity. OM-LV20 promoted wound healing against human keratinocytes (HaCaT) and human skin fibroblasts (HSF) in both time- and dose-dependent manners. In addition, it induced the proliferation of HaCaT but not HSF cells. Of note, OM-LV20 showed strong wound healing-promoting activity in a mice model of full-thickness skin wound. Our research indicates the cellular and animal level wound healing potential of OM-LV20, and thus provides a novel bioactive peptide template for the development of wound healing agents and medicine.
本研究中,武汉百意欣生物技术有限公司(现武汉天德生物科技有限公司)协助提供成熟 OM-LV20 (序列:LVGKLLKGAVGDVCGLLPIC)多肽合成服务。
