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首页> 美国卫生研究院文献>other >The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing?
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The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing?

机译：青蛙皮肤衍生的抗菌肽Esculentin-1a（1-21）NH2以EGF受体依赖的方式促进人类HaCaT角质形成细胞的迁移：人类皮肤伤口愈合的新型促进剂？

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摘要

One of the many functions of skin is to protect the organism against a wide range of pathogens. Antimicrobial peptides (AMPs) produced by the skin epithelium provide an effective chemical shield against microbial pathogens. However, whereas antibacterial/antifungal activities of AMPs have been extensively characterized, much less is known regarding their wound healing-modulatory properties. By using an in vitro re-epithelialisation assay employing special cell-culture inserts, we detected that a derivative of the frog-skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, significantly stimulates migration of immortalized human keratinocytes (HaCaT cells) over a wide range of peptide concentrations (0.025–4 μM), and this notably more efficiently than human cathelicidin (LL-37). This activity is preserved in primary human epidermal keratinocytes. By using appropriate inhibitors and an enzyme-linked immunosorbent assay we found that the peptide-induced cell migration involves activation of the epidermal growth factor receptor and STAT3 protein. These results suggest that esculentin-1a(1-21)NH2 now deserves to be tested in standard wound healing assays as a novel candidate promoter of skin re-epithelialisation. The established ability of esculentin-1a(1-21)NH2 to kill microbes without harming mammalian cells, namely its high anti-Pseudomonal activity, makes this AMP a particularly attractive candidate wound healing promoter, especially in the management of chronic, often Pseudomonas-infected, skin ulcers.
机译：皮肤的多种功能之一是保护生物体免受各种病原体的侵害。皮肤上皮细胞产生的抗菌肽（AMP）提供了有效的化学屏障，可抵御微生物病原体。然而，尽管已经广泛地表征了AMP的抗菌/抗真菌活性，但是关于其伤口愈合调节特性的了解却很少。通过使用采用特殊细胞培养插入物的体外再上皮化测定，我们检测到了青蛙皮肤AMP esculentin-1a的衍生物esculentin-1a（1-21）NH2，可显着刺激永生化的人类角质形成细胞的迁移（ HaCaT细胞）在很宽的肽浓度范围内（0.025–4μM），并且比人导管素（LL-37）更有效。这种活性保留在原代人表皮角质形成细胞中。通过使用适当的抑制剂和酶联免疫吸附测定，我们发现肽诱导的细胞迁移涉及表皮生长因子受体和STAT3蛋白的激活。这些结果表明，esculentin-1a（1-21）NH2现在值得作为新的皮肤上皮上皮候选启动子在标准伤口愈合试验中进行测试。 esculentin-1a（1-21）NH2具有稳定的杀灭微生物而不损害哺乳动物细胞的能力，即其高的抗假单胞菌活性，使该AMP成为特别有吸引力的候选伤口愈合促进剂，尤其是在治疗慢性（通常为假单胞菌-感染，皮肤溃疡。

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