生物谷報道：研究人員在5月在線出版的《自然—細胞生物學》（Nature Cell Biology）期刊上報告說,，一種名為Caspase—14的蛋白質與皮膚抗紫外線損害和水分流失的保護層的形成有關。
Caspase是指(ICE)/CED—3半胱氨酸蛋白酶家族, 目前有14個基因被證實屬于Caspase家族, 包括Caspase—1~Caspase—14, 其中人類有11種: Caspase—1~Caspase—10,、Caspase—13,，而Caspase—11,、Caspase—12具有種屬特異性, 僅存在于鼠中, Caspase—14是在鼠中被發(fā)現(xiàn)的?？茖W家們早已知道,，蛋白質Caspase家族與細胞的程序化死亡和炎癥的發(fā)生有關，但他們一直沒有鑒別出Caspase—14的功能,。
利用Caspase—14被敲出的小鼠,，Wim Declercq 和同事發(fā)現(xiàn)，Caspase—14負責在表皮的上層集中角蛋白和其他蛋白質,，形成角質層,。角質層是由死亡細胞的殘骸形成的平坦層，它們在皮膚上形成一個保護層,。對前抗角蛋白微絲聚集蛋白形成抗角蛋白微絲聚集蛋白(Fillagrin)過程的控制,，保證了上皮的完整性。缺失Caspase—14的小鼠的皮膚出現(xiàn)了角質層缺陷,，這些小鼠更容易出現(xiàn)失水,，也更容易受到紫外線損傷。
原始出處:
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
1 Department for Molecular Biomedical Research, VIB, Technologie Park 927, B-9052, Ghent, Belgium.
2 Department of Molecular Biology, Ghent University, Technologie Park 927, B-9052, Ghent, Belgium.
3 Department of Pathology, Ghent University, De Pintelaan 185, B-9000, Ghent, Belgium.
4 Department of Medical Protein Research, VIB, A. Bartsoenkaai 3, B-9000, Ghent, Belgium.
5 Department of Biochemistry, Ghent University, A. Bartsoenkaai 3, B-9000, Ghent, Belgium.
6 Department of Anatomy, Embryology, Histology, Medical Physics, Ghent University, De Pintelaan 185, B-9000, Ghent, Belgium.
7 Department of Dermatology, Free University of Brussels (VUB), Laarbeeklaan 101, B-1090, Brussels, Belgium.
8 Department of Biology, Ghent University, K. L. Ledeganckstraat 35, B-9000, Ghent, Belgium.
9 Department of Oral Biology and Medicine (Dermatology) University of Washington, 1959 NE Pacific Street, Seattle, WA 98195-7132, USA.
10 Department of Molecular and Cellular Medicine, University of Leuven, and Thromb-X N.V., Herestraat 49, B-3000, Leuven, Belgium.
Correspondence should be addressed to Peter Vandenabeele [email protected] or Wim Declercq [email protected]
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.
