Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), CNRS, INSERM, University Paul Sabatier, University of Toulouse, Toulouse, France.
IFF-Lucas Meyer Cosmetics, Toulouse, France.
Exp Dermatol. 2024 Oct;33(10):e15191. doi: 10.1111/exd.15191.
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.
角蛋白包膜（CE）成分表达的变化是许多病理皮肤状况和衰老的标志，这突显了这一表皮屏障结构在表皮屏障稳态中的重要性。我们对晚期角蛋白包膜蛋白家族的成员 LCE6A 进行了详细的表征。免疫组织化学和免疫印迹实验证实，LCE6A 在表皮分化过程中晚期表达。无论是在人体皮肤切片上进行的重组 LCE6A 交联实验，还是在体外进行的实验，都表明 LCE6A 确实是转谷氨酰胺酶的底物，并与 CE 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的这些特性，并增强了经超声处理的 CE 的机械强度。我们设计了 P26，这是一种源自 LCE6A 的仿生肽，在体外也能增强 CE 的稳定性，并在人体皮肤标本和两项双盲和对照临床试验中评估了其保护性能。P26 能够保护皮肤免受屏障破坏，限制因屏障缺陷而造成的损伤，并能改善皮肤老化的迹象，如皮肤紧致度下降和皮肤粗糙度增加。因此，我们对 LCE6A 作为 CE 的组成部分进行的详细表征，使我们能够开发出一种源自 LCE6A 的肽，具有新的和独特的作用模式，作为化妆品成分和药物制剂可能具有很大的应用前景。
