Prolyl Endopeptidase Is Involved in Filaggrinolysis and Cornification.

Autor:	Briot J; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), University of Toulouse, INSERM UMR1291 - CNRS UMR5051, Toulouse, France., Pons C; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), University of Toulouse, INSERM UMR1291 - CNRS UMR5051, Toulouse, France., Foucher A; L'Oréal Research & Innovation, Aulnay-sous-Bois, France., Goudounèche D; Centre de Microscopie Electronique Appliquée à la Biologie (CMEAB), Toulouse III University, Toulouse, France., Gaudenzio N; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), University of Toulouse, INSERM UMR1291 - CNRS UMR5051, Toulouse, France; Genoskin SAS, Toulouse, France., Donovan M; L'Oréal Research & Innovation, Aulnay-sous-Bois, France., Bernard D; L'Oréal Research & Innovation, Aulnay-sous-Bois, France., Méchin MC; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), University of Toulouse, INSERM UMR1291 - CNRS UMR5051, Toulouse, France., Simon M; Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), University of Toulouse, INSERM UMR1291 - CNRS UMR5051, Toulouse, France. Electronic address: michel.simon@inserm.fr.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2025 Jan; Vol. 145 (1), pp. 98-108.e15. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1016/j.jid.2024.04.028
Abstrakt:	FLG is a well-known biomarker of atopic dermatitis and skin dryness. Its full proteolysis (or filaggrinolysis) produces the major constituents of the natural moisturizing factor. Some proteases/peptidases remain to be identified in this multistep process. Mining 16 omics analyses, we identified prolyl endopeptidase (PREP) as a candidate peptidase. Indirect immunofluorescence and confocal analysis demonstrated its localization in the granular and deep cornified layers, where it colocalized with FLG. Tandem mass spectroscopy and fluorescent quenching activity assays showed that PREP cleaved several synthetic peptides derived from the FLG sequence, at the carboxyl side of an internal proline. Deimination of these peptides increased PREP enzymatic efficiency. Specific inhibition of PREP in reconstructed human epidermis using benzyloxycarbonyl-pro-prolinal induced the accumulation of FLG monomers. Downregulation of PREP expression in reconstructed human epidermis using RNA interference confirmed the impact of PREP on FLG metabolism and highlighted a more general role of PREP in keratinocyte differentiation. Indeed, quantitative global proteomic, western blotting, and RT-qPCR analyses showed a strong reduction in the expression of bleomycin hydrolase, known to be involved in filaggrinolysis, and of several other actors of cornification such as loricrin. Consequently, at the functional level, the transepidermal electric resistance was drastically reduced. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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