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Session X : Cell death in cancer Poster X, 25<br />

The secret life of caspase-14<br />

G. Denecker, E. Hoste, T. Hochepied, B. Gilbert, P. Ovaere, K. D’Herde1, C.<br />

V<strong>and</strong>enBroucke, S. Lippens, L. Schoonjans2, C. Libert, P. V<strong>and</strong>enabeele <strong>and</strong> W.<br />

Declercq<br />

Molecular Signalling <strong>and</strong> Cell Death Unit, Department for Molecular Biomedical<br />

Research, Technologiepark 927, B-9052 Ghent-Zwijnaarde (http://www.dmbr.ugent.be),<br />

VIB, Ghent University. E-mail: wim.declercq@dmbr.Ugent.be<br />

1 Department of Anatomy, Embryology, Histology, Medical Physics, Ugent. 2<br />

Department of Transgene Technology, KUL, Leuven, Belgium.<br />

Caspase-14 is expressed in the differentiating keratinocytes of the epidermis <strong>and</strong> the<br />

hairfollicles. In addition, caspase-14 could also be detected in the Hassall's body's of the<br />

thymus. In the skin caspase-14 activation occurs in the uppermost layers of the epidermis <strong>and</strong><br />

correlates with epidermal cornification. To unravel the possible role of caspase-14 during skin<br />

differentiation, we have generated caspase-14-deficient mice. Caspase-14 knock-out mice<br />

were born normally with the expected Mendelian ratio. The absence of caspase-14 protein<br />

was confirmed both by western blot <strong>and</strong> immunohistochemistry. Histological sections of the<br />

back skin <strong>and</strong> thymus of newborn wild-type <strong>and</strong> caspase-14-deficient mice revealed no<br />

macroscopical differences. Immunohistochemical analysis of other early <strong>and</strong> late<br />

differentiation markers demonstrated a normal expression pattern of K1, K10, K14, loricrin,<br />

involucrin <strong>and</strong> filaggrin. However, the skin of caspase-14-deficient mice had a more shiny<br />

appearance <strong>and</strong> showed a lichiniform phenotype. Electron microscopic analysis indicated the<br />

presence of high numbers composite keratohyalin granules in the caspase-14-deficient<br />

epidermis. These granules are normally used as profilaggrin stores. In accordance, caspase-14<br />

mice have an altered profilaggrin-processing pattern. These data argue for a role of caspase-<br />

14 in the final steps of keratinocyte differentiation. Further analysis of different physiological<br />

parameters is ongoing in order to unravel the secret life of caspase-14.<br />

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