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

Full text not available from this repository.

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
Creators:
CreatorsEmailORCIDORCID Put Code
Peters, FlorianUNSPECIFIEDorcid.org/0000-0002-8529-2326UNSPECIFIED
Rahn, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mengel, MarionUNSPECIFIEDorcid.org/0000-0002-4876-008XUNSPECIFIED
Scharfenberg, FrankaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otte, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koudelka, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, Erwin F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haase, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naumann, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tholey, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker-Pauly, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
CELL-MIGRATION; ULTRASTRUCTURAL-LOCALIZATION; EPIDERMAL DIFFERENTIATION; EXTRACELLULAR-MATRIX; MOUSE KERATINOCYTES; EXPRESSION PATTERNS; MOLECULAR-CLONING; SERINE-PROTEASE; HAIR FOLLICLE; ALPHA-SUBUNITMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59215

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item