Peters, Florian ORCID: 0000-0002-8529-2326, Rahn, Sascha, Mengel, Marion
ORCID: 0000-0002-4876-008X, Scharfenberg, Franka, Otte, Anna, Koudelka, Tomas, Wagner, Erwin F., Wunderlich, F. Thomas, Haase, Michael, Naumann, Ronald, Tholey, Andreas and Becker-Pauly, Christoph
(2021).
Syndecan-1 shedding by meprin impairs keratinocyte adhesion and differentiation in hyperkeratosis.
Matrix Biol., 102.
S. 37 - 70.
AMSTERDAM:
ELSEVIER.
ISSN 1569-1802
Abstract
Dysregulation of proteolytic enzymes has huge impact on epidermal homeostasis, which can result in severe pathological conditions such as fibrosis or Netherton syndrome. The metalloprotease meprin [3 was found to be upregulated in hyperproliferative skin diseases. AP-1 transcription factor complex has been reported to induce Mep1b expression. Since AP-1 and its subunit fos-related antigen 2 (fra-2) are associated with the onset and progression of psoriasis, we wanted to investigate if this could partially be attributed to increased meprin [3 activity. Here, we demonstrate that fra-2 transgenic mice show increased meprin [3 expression and proteolytic activity in the epidermis. To avoid influence by other fra-2 regulated genes, we additionally generated a mouse model that enabled tamoxifen-inducible expression of meprin [3 under the Krt5-promotor to mimic the pathological condition. Interestingly, induced meprin [3 expression in the epidermis resulted in hyperkeratosis, hair loss and mottled pigmentation of the skin. Employing N-terminomics revealed syndecan1 as a substrate of meprin [3 in skin. Shedding of syndecan-1 at the cell surface caused delayed calcium induced differentiation and impaired adhesion of keratinocytes, which was blocked by the meprin [3 inhibitor fetuin-B. (c) 2021 Elsevier B.V. All rights reserved.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-592158 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1016/j.matbio.2021.08.002 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Matrix Biol. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Volume: | 102 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Page Range: | S. 37 - 70 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Date: | 2021 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Publisher: | ELSEVIER | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Place of Publication: | AMSTERDAM | ||||||||||||||||||||||||||||||||||||||||||||||||||||
ISSN: | 1569-1802 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Uncontrolled Keywords: |
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URI: | http://kups.ub.uni-koeln.de/id/eprint/59215 |
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