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Licensed Unlicensed Requires Authentication Published by De Gruyter November 13, 2012

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

  • Maria Arampatzidou , André Schütte , Gunnar C. Hansson , Paul Saftig and Klaudia Brix EMAIL logo
From the journal Biological Chemistry

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.


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

Received: 2012-5-15
Accepted: 2012-9-19
Published Online: 2012-11-13
Published in Print: 2012-12-01

©2012 by Walter de Gruyter Berlin Boston

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