Expression of the human Cathepsin L inhibitor hurpin in mice: skin alterations and increased carcinogenesis

    August 2007 in “ Experimental Dermatology
    Markus Walz, Sabine Kellermann, Matilda Bylaitė, Birgit Andrée, Ulrich Rüther, Ralf Paus, Jennifer E. Kloepper, J. Reifenberger, Thomas Ruzicka
    TLDR Overexpression of hurpin in mice leads to abnormal skin and higher skin cancer risk.
    The study investigated the effects of the serine protease inhibitor hurpin on skin by generating transgenic mice expressing human hurpin. Hurpin, which inhibits the cysteine protease Cathepsin L, was overexpressed in psoriatic skin and increased keratinocyte resistance to UVB-induced apoptosis. Transgenic mice exhibited abnormal abdominal fur and reduced apoptosis after UV exposure compared to wild-type mice. Notably, these mice showed increased susceptibility to skin cancer following chemical carcinogenesis. Gene expression analysis indicated differences in antigen presentation and angiogenesis between transgenic and wild-type mice. The findings suggested that hurpin's regulation of Cathepsin L played a significant role in skin alterations and carcinogenesis, potentially relevant to human skin diseases.
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