Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis.

Autor:	Peters F; Department of Dermatology, University of Cologne, Cologne, Germany; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany. Electronic address: franziska.peters@uk-koeln.de., Tellkamp F; Department of Dermatology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Current Address: Institute for Genetics, University of Cologne, Cologne, Germany., Brodesser S; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany., Wachsmuth E; Department of Dermatology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Tosetti B; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany., Karow U; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany., Bloch W; Department of Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany., Utermöhlen O; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Krönke M; Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Niessen CM; Department of Dermatology, University of Cologne, Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2020 Oct; Vol. 140 (10), pp. 1927-1937.e5. Date of Electronic Publication: 2020 Feb 22.
DOI:	10.1016/j.jid.2020.02.006
Abstrakt:	Epidermal barrier dysfunction is associated with a wide range of highly prevalent inflammatory skin diseases. However, the molecular processes that drive epidermal barrier maintenance are still largely unknown. Here, using quantitative proteomics, lipidomics, and mouse genetics, we characterize epidermal barrier maintenance versus a newly established barrier and functionally identify differential ceramide synthase 4 protein expression as one key difference. We show that epidermal loss of ceramide synthase 4 first disturbs epidermal lipid metabolism and adult epidermal barrier function, ultimately resulting in chronic skin barrier disease characterized by acanthosis, hyperkeratosis, and immune cell accumulation. Importantly, prolonged barrier dysfunction induced by loss of ceramide synthase 4 induced a barrier repair response that largely recapitulates molecular programs of barrier establishment. Collectively, this study provides an unbiased temporal proteomic characterization of barrier maintenance and disturbed homeostasis and shows that lipid homeostasis is essential to maintain adult skin barrier function to prevent disease. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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