Strengthening the Skin Barrier by Using a Late Cornified Envelope 6A-Derived Biomimetic Peptide

IF 3.5 3区 医学 Q1 DERMATOLOGY
Mikaël Pancarte, Julie Leignadier, Séverine Courrech, Guy Serre, Joan Attia, Nathalie Jonca
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Abstract

Changes in the expression of cornified envelope (CE) components are a hallmark of numerous pathological skin conditions and aging, underlying the importance of this stratum corneum structure in the homeostasis of the epidermal barrier. We performed a detailed characterisation of LCE6A, a member of the Late Cornified Envelope protein family. Immunohistochemical and immunoblot experiments confirmed that LCE6A is expressed late during epidermal differentiation. Crosslinking assays of recombinant LCE6A performed either in situ on human skin sections or in vitro demonstrated that LCE6A is indeed a substrate of transglutaminases and crosslinked to CEs. LCE6A-derived peptides containing a glutamine-lysine sequence retained these properties of the full-length protein and reinforced the mechanical resistance of CE submitted to sonication. We designed P26, a LCE6A-derived biomimetic peptide that similarly reinforced CE in vitro, and evaluated its protective properties ex vivo, on human skin explants, and in two double blind and vehicle-controlled clinical trials. P26 was able to protect the skin from barrier disruption, to limit the damage resulting from a defective barrier, and could improve the signs of aging such as loss of skin firmness and increased skin roughness. Hence, our detailed characterisation of LCE6A as a component of the CE enabled us to develop a LCE6A-derived peptide, biologically active with a new and original mode of action that could be of great interest as a cosmetic ingredient and a pharmacologic agent.

Abstract Image

使用晚玉米化包膜 6A 衍生的生物仿生肽强化皮肤屏障
粟粒化包膜(CE)成分表达的变化是许多病理皮肤状况和衰老的标志,这说明了角质层结构在表皮屏障平衡中的重要性。我们对晚期角质化包膜蛋白家族的成员 LCE6A 进行了详细表征。免疫组织化学和免疫印迹实验证实,LCE6A 在表皮分化过程中表达较晚。在人体皮肤切片上原位或体外进行的重组 LCE6A 交联试验表明,LCE6A 确实是转谷氨酰胺酶的底物,并与 CEs 交联。含有谷氨酰胺-赖氨酸序列的 LCE6A 衍生肽保留了全长蛋白质的这些特性,并增强了 CE 在超声作用下的机械阻力。我们设计了一种 LCE6A 衍生生物仿生肽 P26,它在体外同样能增强 CE,我们还在人体皮肤外植体上以及两项双盲和药物对照临床试验中评估了它的体内保护特性。P26 能够保护皮肤免受屏障破坏,限制屏障缺陷造成的损害,并能改善皮肤老化迹象,如皮肤紧致度下降和皮肤粗糙度增加。因此,我们对作为 CE 组成部分的 LCE6A 进行了详细的表征,从而开发出了一种源自 LCE6A 的多肽,这种多肽具有生物活性和新颖的作用模式,可作为化妆品成分和药剂发挥巨大的作用。
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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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