Are melanocortin peptides future therapeutics for cutaneous wound healing?
Are melanocortin peptides future therapeutics for cutaneous wound healing?
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DOI：
10.1111/exd.13887
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发表时间：
2019-03-01
影响因子：
3.6
通讯作者：
Luger, Thomas
中科院分区：
文献类型：
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作者：
Boehm, Markus;Luger, Thomas
皮肤伤口愈合是一个复杂的过程，分为不同的阶段，即炎症，增殖和重塑阶段。在这些阶段，各种常驻皮肤细胞类型以及免疫系统细胞协调愈合过程。在过去的一年中，已经表明大多数皮肤细胞类型表达黑皮质素1受体（MC 1 R），其以高亲和力和elevently多效性生物学效应结合α-黑素细胞刺激激素（α-MSH），例如调节炎症和免疫应答、细胞保护、抗氧化防御和胶原蛋白周转。已发现截短的α-MSH肽如Lys-Pro-瓦尔（KPV）以及衍生物如Lys-D-Pro-Thr（KdPT）（后者含有白细胞介素-1 β的氨基酸序列193-195）具有抗炎作用，但缺乏α-MSH的色素诱导活性。我们在这里提出，这样的肽是有前途的未来候选人治疗皮肤伤口和皮肤溃疡。在硅片，在体外，离体和动物模型的实验方法进行了概述。这是其次是一个公正的讨论，这样的肽作为未来的候选人皮肤伤口的治疗管理和审查的黑皮质素肽和衍生物在伤口愈合的迄今可用的数据的正反论点。
Cutaneous wound healing is a complex process divided into different phases, that is an inflammatory, proliferative and remodelling phase. During these phases, a variety of resident skin cell types but also cells of the immune system orchestrate the healing process. In the last year, it has been shown that the majority of cutaneous cell types express the melanocortin 1 receptor (MC1R) that binds alpha-melanocyte-stimulating hormone (alpha-MSH) with high affinity and elicits pleiotropic biological effects, for example modulation of inflammation and immune responses, cytoprotection, antioxidative defense and collagen turnover. Truncated alpha-MSH peptides such as Lys-Pro-Val (KPV) as well as derivatives like Lys-D-Pro-Thr (KdPT), the latter containing the amino acid sequence 193-195 of interleukin-1 beta, have been found to possess anti-inflammatory effects but to lack the pigment-inducing activity of alpha-MSH. We propose here that such peptides are promising future candidates for the treatment of cutaneous wounds and skin ulcers. Experimental approaches in silico, in vitro, ex vivo and in animal models are outlined. This is followed by an unbiased discussion of the pro and contra arguments of such peptides as future candidates for the therapeutic management of cutaneous wounds and a review of the so-far available data on melanocortin peptides and derivatives in wound healing.