Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis
| Autor: | Olaf Utermöhlen, Bettina Tosetti, Susanne Brodesser, Frederik Tellkamp, Ulrike Karow, Franziska Peters, E. Wachsmuth, Martin Krönke, Wilhelm Bloch, Carien M. Niessen |
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| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Cell Regulator Acanthosis Dermatology Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Immune system Sphingosine N-Acyltransferase Keratin Morphogenesis medicine Animals Homeostasis Molecular Biology Ceramide synthase Skin chemistry.chemical_classification integumentary system Lipid metabolism Cell Biology Lipid Metabolism medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Epidermis |
| Zdroj: | Journal of Investigative Dermatology. 140:1927-1937.e5 |
| ISSN: | 0022-202X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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