Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing.
Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing.
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Cathelicidin-OA1 是一种从两栖动物中鉴定出的新型抗氧化肽，可加速皮肤伤口愈合
DOI：
10.1038/s41598-018-19486-9
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发表时间：
2018-01-17
影响因子：
4.6
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Cao X;Wang Y;Wu C;Li X;Fu Z;Yang M;Bian W;Wang S;Song Y;Tang J;Yang X
放线菌素在寄主防御中起着关键作用。新的排泄素的发现是一项重要的研究；然而，尽管在脊椎动物中发现了许多排泄素，但在两栖动物中却鲜有报道。在这里，我们从两栖动物Odorrana andersonii的皮肤中鉴定出一种新的放线菌素(命名为cuselicidin-OA1)。长春花素-OA1由一个198个残基的前肽翻译后加工而成，其氨基酸序列为‘IGRDPTWSHLAASCLKIFDDLPKTHN’，相对分子质量为3038.5 Da。功能分析表明，与其他放线菌素不同，放线菌素-OA1没有直接杀菌、急性毒性和溶血活性，但具有抗氧化活性。重要的是，放线菌素-OA1以时间和剂量依赖的方式加速了对人角质形成细胞(HaCaT)和皮肤成纤维细胞(HSF)的伤口愈合。值得注意的是，长春新碱-OA1还在全层皮肤创伤的小鼠模型中显示出促进伤口愈合的作用，通过促进巨噬细胞到伤口部位的募集，诱导HaCaT细胞增殖和HSF细胞迁移，加速了再上皮化和肉芽组织的形成。这是从两栖动物中鉴定出的第一种具有强大伤口愈合活性的长春花素。这些结果将有助于开发新型创面愈合剂，并有助于我们了解长春花素的生物学功能。
Cathelicidins play pivotal roles in host defense. The discovery of novel cathelicidins is important research; however, despite the identification of many cathelicidins in vertebrates, few have been reported in amphibians. Here we identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an amphibian species,Odorrana andersonii. Produced by posttranslational processing of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence of ‘IGRDPTWSHLAASCLKCIFDDLPKTHN′ and a molecular mass of 3038.5 Da. Functional analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing promotion in a mouse model with full-thickness skin wounds, accelerating re-epithelialization and granulation tissue formation by enhancing the recruitment of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell migration. This is the first cathelicidin identified from an amphibian that shows potent wound-healing activity. These results will help in the development of new types of wound-healing agents and in our understanding of the biological functions of cathelicidins.