Nature 子刊： Caspase-14与皮肤保护层的形成有关

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Nature 子刊： Caspase-14与皮肤保护层的形成有关 研究人员在5月在线出版的《自然—细胞生物学》（NatureCellBiology）期刊上报告说，一种名为Caspase—14的蛋白质与皮肤抗紫外线损害和水分流失的保护层的形成有关。Caspase是指(ICE)/CED—3半胱氨酸蛋白酶家族,目前有14个基因被证实属于Caspase家族,包括Caspase—1~Caspase—14,其中人类有11种:Caspase—1~Caspase—10、Casp
http://www.bioon.com 生 物 谷 网 站  生物谷报道：研究人员在5月在线出版的《自然—细胞生物学》（Nature Cell Biology）期刊上报告说，一种名为Caspase—14的蛋白质与皮肤抗紫外线损害和水分流失的保护层的形成有关。

   Caspase是指(ICE)/CED—3半胱氨酸蛋白酶家族, 目前有14个基因被证实属于Caspase家族, 包括Caspase—1~Caspase—14, 其中人类有11种: Caspase—1~Caspase—10、Caspase—13，而Caspase—11、Caspase—12具有种属特异性, 仅存在于鼠中, Caspase—14是在鼠中被发现的。科学家们早已知道，蛋白质Caspase家族与细胞的程序化死亡和炎症的发生有关，但他们一直没有鉴别出Caspase—14的功能。

  利用Caspase—14被敲出的小鼠，Wim Declercq 和同事发现，Caspase—14负责在表皮的上层集中角蛋白和其他蛋白质，形成角质层。角质层是由死亡细胞的残骸形成的平坦层，它们在皮肤上形成一个保护层。对前抗角蛋白微丝聚集蛋白形成抗角蛋白微丝聚集蛋白(Fillagrin)过程的控制，保证了上皮的完整性。缺失Caspase—14的小鼠的皮肤出现了角质层缺陷，这些小鼠更容易出现失水，也更容易受到紫外线损伤。

原始出处:

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, Jo雔 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 peter.vandenabeele@dmbr.ugent.be or Wim Declercq wim.declercq@dmbr.ugent.be

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.