Mikaël Pancarte, Julie Leignadier, Séverine Courrech, Guy Serre, Joan Attia, Nathalie Jonca
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引用次数: 0
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.
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.