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

Journal article
Authors Maria Arampatzidou
André Schütte
Gunnar C. Hansson
Paul Saftig
Klaudia Brix
Published in Biological chemistry
Volume 393
Issue 12
Pages 1391-403
ISSN 1437-4315
Publication year 2012
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1391-403
Language en
Links dx.doi.org/10.1515/hsz-2012-0204
Keywords Animals, Cadherins, analysis, metabolism, Cathepsin B, metabolism, Cathepsin K, genetics, metabolism, Cathepsin L, metabolism, Colon, metabolism, ultrastructure, Extracellular Matrix, metabolism, Gene Deletion, Intercellular Junctions, metabolism, ultrastructure, Intestinal Mucosa, metabolism, ultrastructure, Male, Mice, Mice, Inbred C57BL, Occludin, analysis, metabolism, Proteolysis
Subject categories Basic Medicine

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.

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