Universität zu Köln

Peters, Franziska ORCID: 0000-0002-3250-3740, Tellkamp, Frederik ORCID: 0000-0002-0473-7320, Brodesser, Susanne, Wachsmuth, Emmi ORCID: 0000-0002-4416-3392, Tosetti, Bettina, Karow, Ulrike ORCID: 0000-0003-3577-6020, Bloch, Wilhelm, Utermoehlen, Olaf, Kroenke, Martin and Niessen, Carien M. (2020). Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis. J. Invest. Dermatol., 140 (10). S. 1927 - 1943. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Peters, Franziska UNSPECIFIED orcid.org/0000-0002-3250-3740 UNSPECIFIED Tellkamp, Frederik UNSPECIFIED orcid.org/0000-0002-0473-7320 UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wachsmuth, Emmi UNSPECIFIED orcid.org/0000-0002-4416-3392 UNSPECIFIED Tosetti, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Karow, Ulrike UNSPECIFIED orcid.org/0000-0003-3577-6020 UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-317527
DOI:	10.1016/j.jid.2020.02.006
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	140
Number:	10
Page Range:	S. 1927 - 1943
Date:	2020
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STRATUM-CORNEUM; STEM-CELLS; FOLLICLE; LIPIDS; ICHTHYOSIS Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31752