title: Caspase-14-deficient mice are more prone to the development of parakeratosis.
abstract: Caspase-14 is an important protease in the proper formation of a fully functional skin barrier. Newborn mice that are deficient in caspase-14 exhibit increased transepidermal water loss and are highly sensitive to UVB-induced photodamage. Decreased caspase-14 expression and incomplete caspase-14 processing in lesional psoriatic parakeratotic stratum corneum has been reported previously. In this study, we show that caspase-14-deficient skin frequently displays incompletely cornified cells in the transitional zone between the granular and the cornified layers, pointing to a delay in cornification. We also demonstrate that after challenge of epidermal permeability barrier function by repetitive acetone treatment, a higher incidence of large parakeratotic plaques was observed in caspase-14-deficient skin. Furthermore, caspase-14-deficient mice are more prone than control mice to the development of parakeratosis upon induction of psoriasis-like dermatitis by imiquimod treatment. These results show that lack of caspase-14 expression predisposes to the development of parakeratosis and that caspase-14 has an important role in keratinocyte terminal differentiation and the maintenance of normal stratum corneum, especially in conditions causing epidermal hyperproliferation.
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Esther
authors.initials: E
authors.lastname: Hoste
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Geertrui
authors.initials: G
authors.lastname: Denecker
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gilbert
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Nieuwerburgh
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Leslie
authors.initials: L
authors.lastname: van der Fits
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Bob
authors.initials: B
authors.lastname: Asselbergh
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Riet
authors.initials: R
authors.lastname: De Rycke
authors.affiliation: Department of Dermatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hachem
authors.affiliation: Laboratory of Pharmaceutical Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Dieter
authors.initials: D
authors.lastname: Deforce
authors.affiliation: Department of Dermatology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Errol P
authors.initials: EP
authors.lastname: Prens
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
authors.affiliation: Molecular Signaling and Cell Death Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium. Electronic address: wim.declercq@dmbr.vib-UGent.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Declercq
mesh_terms: D000634:Aminoquinolines / Q000009:adverse effects; D000818:Animals; D020169:Caspases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D000077271:Imiquimod; D015603:Keratinocytes / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D010241:Parakeratosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D011565:Psoriasis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
chemical_list: D000634:Aminoquinolines; C506449:Casp14 protein, mouse; D020169:Caspases; D000077271:Imiquimod