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

Markus Walz, Sabine Kellermann, Matilda Bylaite, Birgit Andrée, Ulrich Rüther, Ralf Paus, Jennifer E. Kloepper, Julia Reifenberger, Thomas Ruzicka

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The serine protease inhibitor (serpin) hurpin (serpin B13) is a cross class-specific inhibitor of the cysteine protease Cathepsin (Cat) L. Cat L is involved in lysosomal protein degradation, hair follicle morphogenesis, epidermal differentiation and epitope generation of antigens. Hurpin is a 44 kDa protein which is expressed predominantly in epidermal cells. In psoriatic skin samples, hurpin was strongly overexpressed when compared with normal skin. Keratinocytes overexpressing hurpin showed increased resistance towards UVB-induced apoptosis. To further analyse the functional importance of this inhibitor, we have generated transgenic mice with deregulated Cat L activity by expressing human hurpin in addition to the endogenous mouse inhibitor. The three independent transgenic lines generated were characterized by identical effects excluding insertional phenotypes. Macroscopically, mice expressing human hurpin are characterized by abnormal abdominal fur. The number of apoptotic cells and caspase-3 positive cells was reduced after UV-irradiation in transgenic animals compared with wild-type mice. Interestingly, after chemical carcinogenesis, transgenic mice showed an increased susceptibility to develop skin cancer. Array analysis of gene expression revealed distinct differences between wild-type and hurpin-transgenic mice. Among others, differentially expressed genes are related to antigen presentation and angiogenesis. These results suggest an important role of Cat L regulation by hurpin which might be of clinical relevance in human skin diseases.

Original languageEnglish (US)
Pages (from-to)715-723
Number of pages9
JournalExperimental Dermatology
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

Fingerprint

Cathepsin L
Skin
Carcinogenesis
Transgenic Mice
Serine Proteinase Inhibitors
Cells
Cysteine Proteinase Inhibitors
Antigens
Genetically Modified Animals
Hair Follicle
Antigen Presentation
Skin Neoplasms
Morphogenesis
Keratinocytes
Skin Diseases
Gene expression
Human Activities
Caspase 3
Proteolysis
Epitopes

Keywords

  • Array analysis
  • Cathepsin L inhibitor
  • Hurpin
  • Skin cancer
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Expression of the human Cathepsin L inhibitor hurpin in mice : Skin alterations and increased carcinogenesis. / Walz, Markus; Kellermann, Sabine; Bylaite, Matilda; Andrée, Birgit; Rüther, Ulrich; Paus, Ralf; Kloepper, Jennifer E.; Reifenberger, Julia; Ruzicka, Thomas.

In: Experimental Dermatology, Vol. 16, No. 9, 01.09.2007, p. 715-723.

Research output: Contribution to journalArticle

Walz, M, Kellermann, S, Bylaite, M, Andrée, B, Rüther, U, Paus, R, Kloepper, JE, Reifenberger, J & Ruzicka, T 2007, 'Expression of the human Cathepsin L inhibitor hurpin in mice: Skin alterations and increased carcinogenesis', Experimental Dermatology, vol. 16, no. 9, pp. 715-723. https://doi.org/10.1111/j.1600-0625.2007.00579.x
Walz, Markus ; Kellermann, Sabine ; Bylaite, Matilda ; Andrée, Birgit ; Rüther, Ulrich ; Paus, Ralf ; Kloepper, Jennifer E. ; Reifenberger, Julia ; Ruzicka, Thomas. / Expression of the human Cathepsin L inhibitor hurpin in mice : Skin alterations and increased carcinogenesis. In: Experimental Dermatology. 2007 ; Vol. 16, No. 9. pp. 715-723.
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