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Journal Article

Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis.


Naumann,  Ronald
Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society;

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Peters, F., Rahn, S., Mengel, M., Scharfenberg, F., Otte, A., Koudelka, T., et al. (2021). Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis. Matrix biology: journal of the International Society for Matrix Biology, 102, 37-69. doi:10.1016/j.matbio.2021.08.002.

Cite as: https://hdl.handle.net/21.11116/0000-000A-0BC1-0
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 β 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 β activity. Here, we demonstrate that fra-2 transgenic mice show increased meprin β 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 β under the Krt5-promotor to mimic the pathological condition. Interestingly, induced meprin β expression in the epidermis resulted in hyperkeratosis, hair loss and mottled pigmentation of the skin. Employing N-terminomics revealed syndecan-1 as a substrate of meprin β 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 β inhibitor fetuin-B.