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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

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Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon

Maria Arampatzidou1 / André Schütte2 / Gunnar C. Hansson2 / Paul Saftig3 / 1

1School of Engineering and Science, Research Center MOLIFE – Molecular Life Science, Jacobs University Bremen, Campus Ring 6, D-28759 Bremen, Germany

2Department of Medical Biochemistry, University of Gothenburg, Medicinaregatan 9A, S-41390 Gothenburg, Sweden

3Institute of Biochemistry, Christian-Albrechts Universität zu Kiel, Olshausenstraße 40, D-24118 Kiel, Germany

Corresponding author: Klaudia Brix, School of Engineering and Science, Research Center MOLIFE – Molecular Life Science, Jacobs University Bremen, Campus Ring 6, D-28759 Bremen, Germany

Citation Information: Biological Chemistry. Volume 393, Issue 12, Pages 1391–1403, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/hsz-2012-0204, November 2012

Publication History

Received:
2012-05-15
Accepted:
2012-09-19
Published Online:
2012-11-13

Abstract

Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory activities in the mouse colon. To further elucidate its role, we used Ctsk-/- mice and demonstrated that the absence of cathepsin K was accompanied by elevated protein levels of related cysteine cathepsins (cathepsins B, L, and X) in the colon. In principle, such changes could result in altered subcellular localization; however, the trafficking of cysteine cathepsins was not affected in the colon of Ctsk-/- mice. However, cathepsin K deficiency affected the extracellular matrix constituents, as higher amounts of collagen IV and laminin were observed. Moreover, the localization pattern of the intercellular junction proteins E-cadherin and occludin was altered in the colon of Ctsk-/- mice, suggesting potential impairment of the barrier function. Thus, we used an ex vivo method for assessing the mucus layers and showed that the absence of cathepsin K had no influence on mucus organization and growth. The data of this study support the notion that cathepsin K contributes to intestinal homeostasis and tissue architecture, but the lack of cathepsin K activity is not expected to affect the mucus-depending barrier functions of the mouse colon. These results are important with regard to oral administration of cathepsin K inhibitors that are currently under investigation in clinical trials.

Keywords: cysteine cathepsins; colon; intercellular junctions; intestinal barrier; mucus

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