title: Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon.
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.affiliation: School of Engineering and Science, ResearchCenter MOLIFE – Molecular Life Science, Jacobs University Bremen, Campus Ring 6, D-28759 Bremen , Germany
authors.forename: Maria
authors.initials: M
authors.lastname: Arampatzidou
authors.forename: André
authors.initials: A
authors.lastname: Schütte
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
mesh_terms: D000818:Animals; D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D056657:Cathepsin K / Q000235:genetics* / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism*; D017353:Gene Deletion; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D062793:Occludin / Q000032:analysis / Q000378:metabolism; D059748:Proteolysis
chemical_list: D015820:Cadherins; D062793:Occludin; D002401:Cathepsin B; D056668:Cathepsin L; D056657:Cathepsin K