Letter abstract
Nature Cell Biology 9, 666 - 674 (2007)
Published online: 21 May 2007 | doi:10.1038/ncb1597
Caspase-14 protects against epidermal UVB photodamage and water loss
Geertrui Denecker1,2, Esther Hoste1,2, Barbara Gilbert1,2, Tino Hochepied1,2, Petra Ovaere1,2, Saskia Lippens1,2, Caroline Van den Broecke3, Petra Van Damme4,5, Katharina D'Herde6, Jean-Pierre Hachem7, Gaetan Borgonie8, Richard B. Presland9, Luc Schoonjans10, Claude Libert1,2, Joël Vandekerckhove4,5, Kris Gevaert4,5, Peter Vandenabeele1,2 & Wim Declercq1,2
Caspase-14 belongs to a conserved family of aspartate-specific proteinases. Its expression is restricted almost exclusively to the suprabasal layers of the epidermis and the hair follicles1, 2, 3, 4. Moreover, the proteolytic activation of caspase-14 is associated with stratum corneum formation, implicating caspase-14 in terminal keratinocyte differentiation and cornification5, 6. Here, we show that the skin of caspase-14-deficient mice was shiny and lichenified, indicating an altered stratum-corneum composition. Caspase-14-deficient epidermis contained significantly more alveolar keratohyalin F-granules, the profilaggrin stores. Accordingly, caspase-14-deficient epidermis is characterized by an altered profilaggrin processing pattern and we show that recombinant caspase-14 can directly cleave profilaggrin in vitro. Caspase-14-deficient epidermis is characterized by reduced skin-hydration levels and increased water loss. In view of the important role of filaggrin in the structure and moisturization of the skin, the knockout phenotype could be explained by an aberrant processing of filaggrin. Importantly, the skin of caspase-14-deficient mice was highly sensitive to the formation of cyclobutane pyrimidine dimers after UVB irradiation, leading to increased levels of UVB-induced apoptosis. Removal of the stratum corneum indicate that caspase-14 controls the UVB scavenging capacity of the stratum corneum.
- Department for Molecular Biomedical Research, VIB, Technologie Park 927, B-9052, Ghent, Belgium.
- Department of Molecular Biology, Ghent University, Technologie Park 927, B-9052, Ghent, Belgium.
- Department of Pathology, Ghent University, De Pintelaan 185, B-9000, Ghent, Belgium.
- Department of Medical Protein Research, VIB, A. Bartsoenkaai 3, B-9000, Ghent, Belgium.
- Department of Biochemistry, Ghent University, A. Bartsoenkaai 3, B-9000, Ghent, Belgium.
- Department of Anatomy, Embryology, Histology, Medical Physics, Ghent University, De Pintelaan 185, B-9000, Ghent, Belgium.
- Department of Dermatology, Free University of Brussels (VUB), Laarbeeklaan 101, B-1090, Brussels, Belgium.
- Department of Biology, Ghent University, K. L. Ledeganckstraat 35, B-9000, Ghent, Belgium.
- Department of Oral Biology and Medicine (Dermatology) University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-7132, USA.
- Department of Molecular and Cellular Medicine, University of Leuven, and Thromb-X N.V., Herestraat 49, B-3000, Leuven, Belgium.
Correspondence to: Peter Vandenabeele1,2 e-mail: peter.vandenabeele@dmbr.ugent.be
Correspondence to: Wim Declercq1,2 e-mail: wim.declercq@dmbr.ugent.be
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