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