Caspase-14 protects against epidermal UVB photodamage and water loss

Nat Cell Biol. 2007 Jun;9(6):666-74. doi: 10.1038/ncb1597. Epub 2007 May 21.

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 follicles. Moreover, the proteolytic activation of caspase-14 is associated with stratum corneum formation, implicating caspase-14 in terminal keratinocyte differentiation and cornification. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Aging / radiation effects
  • Animals
  • Animals, Newborn
  • Caspases / genetics*
  • Cell Differentiation / genetics
  • Cell Differentiation / radiation effects
  • Cells, Cultured
  • Dehydration / enzymology*
  • Dehydration / physiopathology
  • Epidermis / enzymology*
  • Epidermis / physiopathology
  • Epidermis / radiation effects
  • Intermediate Filament Proteins / metabolism
  • Keratinocytes / enzymology*
  • Keratinocytes / pathology
  • Keratinocytes / radiation effects
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Photosensitivity Disorders / enzymology
  • Photosensitivity Disorders / genetics
  • Photosensitivity Disorders / physiopathology
  • Pyrimidine Dimers / metabolism
  • Ultraviolet Rays / adverse effects*
  • Water-Electrolyte Balance / genetics
  • Water-Electrolyte Balance / radiation effects

Substances

  • Intermediate Filament Proteins
  • Pyrimidine Dimers
  • filaggrin
  • Casp14 protein, mouse
  • Caspases