Caspase-14 protects against epidermal UVB photodamage and water loss

Abstract

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.

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Figure 1: Histomorphological characterization of caspase-14-deficient epidermis.
Figure 2: Caspase-14 mediates profilaggrin processing, and controls transepidermal water loss and stratum corneum hydration.
Figure 3: Caspase-14-deficient mice are highly sensitive to UVB-induced apoptosis.
Figure 4: The UVB-filtering capacity of the stratum corneum is reduced in caspase-14-deficient mice.

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Acknowledgements

We thank A. Bredan for editing the manuscript and E. van Damme, A. Meeus and W. Deckers for technical assistance. This work was supported in part by the Interuniversitaire Attractiepolen V, the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, the Epistem 6th framework EC-RTD grant and Ghent University GOA project. G.D. is a postdoctoral fellow at the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, E.H. has an Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie (IWT) predoctoral grant and P.O. had an Emmanuel Verscheuren and an IWT predoctoral grant. R.P. was supported by R01 AR49183 from the National Institutes of Health.

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Correspondence to Peter Vandenabeele or Wim Declercq.

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Denecker, G., Hoste, E., Gilbert, B. et al. Caspase-14 protects against epidermal UVB photodamage and water loss. Nat Cell Biol 9, 666–674 (2007). https://doi.org/10.1038/ncb1597

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