Regulation of keratinocyte proliferation and epidermal inflammation by meprin α–mediated cleavage of dermokine
Dysregulations within the epidermal proteolytic network can cause hyperproliferative and inflammatory disorders. Although the metalloprotease meprin α is localized in the stratum basale in healthy skin, increased levels are found in the upper epidermal layers in wound healing and psoriatic lesions. To investigate a link between meprin α expression and keratinocyte proliferation, we developed a mouse model for inducible expression of pathological meprin α levels (ie, K5Mα mice). K5Mα mice developed a skin phenotype characterized by hyperkeratosis, acanthosis, parakeratosis, and barrier defect. Keratinocyte hyperproliferation and local inflammation were induced upon induction of meprin α expression. By N-terminomics, we identified dermokine, a regulator of keratinocyte proliferation and epidermal immune response, as a putative substrate of meprin α. We validated the proteolysis and identified the cleavage site, which is highly conserved in mammals, suggesting that dermokine degradation by meprin α represents a central mechanism in wound healing and hyperproliferative skin diseases.
Authors
- Vahap Canbay (ORCID: https://orcid.org/0000-0002-5218-2315)
- Michaela Schweizer (ORCID: https://orcid.org/0000-0001-5062-328X)
- Fred Armbrust (ORCID: https://orcid.org/0000-0002-3331-5522)
- Silje Beckinger
- Cynthia Bülck (ORCID: https://orcid.org/0000-0002-8354-6177)
- Ronald A. Naumann
- Nathalie Jonca (ORCID: https://orcid.org/0000-0003-3602-0102)
- Neele Schumacher (ORCID: https://orcid.org/0000-0002-8389-0365)
- Florian Peters (ORCID: https://orcid.org/0000-0002-8529-2326)
- Inken Harder (ORCID: https://orcid.org/0000-0002-3079-0440)
- Kira Bickenbach (ORCID: https://orcid.org/0000-0001-5079-0512)
- Konstantinos Kalogeropoulos (ORCID: https://orcid.org/0000-0003-3907-9281)
- Becker-Pauly Christoph
- Marion Mengel (ORCID: https://orcid.org/0000-0002-4876-008X)
- Ulrich auf dem Keller (ORCID: https://orcid.org/0000-0002-3431-7415)
- Malina Rüffer
- Niklas Beck
- Vasco Köhling
- Sascha Rüffer
- Inez Götting
- Marian Lewerenz
- Emil Fries
- Michael Haase
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Universität Hamburg (DE)
- University of Basel (CH)
- Christian-Albrechts-Universität zu Kiel (DE)
- Toulouse Mathematics Institute (FR)
- University Medical Center Hamburg-Eppendorf (DE)
- University Hospital Schleswig-Holstein (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University Hospital Carl Gustav Carus (DE)
- Freie Universität Berlin (DE)
- University of Lübeck (DE)
- Technical University of Denmark (DK)
- Delft University of Technology (NL)
Publication Details
- Journal
- Journal of Investigative Dermatology
- Published
- 2026-02-01
- DOI
- https://doi.org/10.1016/j.jid.2026.01.034
- Primary Topic
- Skin and Cellular Biology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00