Document Detail


Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon.
MedLine Citation:
PMID:  23152408     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Maria Arampatzidou; André Schütte; Gunnar C Hansson; Paul Saftig; Klaudia Brix
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biological chemistry     Volume:  393     ISSN:  1437-4315     ISO Abbreviation:  Biol. Chem.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1391-403     Citation Subset:  IM    
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