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

Artikel i vetenskaplig tidskrift
Författare Maria Arampatzidou
André Schütte
Gunnar C. Hansson
Paul Saftig
Klaudia Brix
Publicerad i Biological chemistry
Volym 393
Nummer/häfte 12
Sidor 1391-403
ISSN 1437-4315
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 1391-403
Språk en
Länkar dx.doi.org/10.1515/hsz-2012-0204
Ämnesord 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
Ämneskategorier Medicinska grundvetenskaper

Sammanfattning

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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