| First Author | Peters F | Year | 2021 |
| Journal | Matrix Biol | Volume | 102 |
| Pages | 37-69 | PubMed ID | 34508852 |
| Mgi Jnum | J:321387 | Mgi Id | MGI:6825658 |
| Doi | 10.1016/j.matbio.2021.08.002 | Citation | Peters F, et al. (2021) Syndecan-1 shedding by meprin beta impairs keratinocyte adhesion and differentiation in hyperkeratosis. Matrix Biol 102:37-69 |
| abstractText | 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 beta 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 beta activity. Here, we demonstrate that fra-2 transgenic mice show increased meprin beta 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 beta under the Krt5-promotor to mimic the pathological condition. Interestingly, induced meprin beta 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 beta 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 beta inhibitor fetuin-B. |
