Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon
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Maria Arampatzidou
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.
©2012 by Walter de Gruyter Berlin Boston
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- Highlight: 29th Winter School on Proteinases and Their Inhibitors
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- Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins
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- Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells
- Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes
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- CLIPPER: an add-on to the Trans-Proteomic Pipeline for the automated analysis of TAILS N-terminomics data
- Review
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- Research Articles/Short Communications
- Genes and Nucleic Acids
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- Protein Structure and Function
- Molecular determinants of human dipeptidyl peptidase III sensitivity to thiol modifying reagents
- Modular structure of HEL protein from Arabidopsis reveals new potential functions for PR-4 proteins
- Proteolysis
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Articles in the same Issue
- Masthead
- Masthead
- Guest Editorial
- Highlight: 29th Winter School on Proteinases and Their Inhibitors
- Highlight: 29th Winter School on Proteinases and their Inhibitors
- Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases
- Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon
- Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins
- Cysteine cathepsins are not critical for TRAIL- and CD95-induced apoptosis in several human cancer cell lines
- Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells
- Overexpression of the urokinase receptor splice variant uPAR-del4/5 in breast cancer cells affects cell adhesion and invasion in a dose-dependent manner and modulates transcription of tumor-associated genes
- IGF-I receptor phosphorylation is impaired in cathepsin X-deficient prostate cancer cells
- Cell surface engineering of renal cell carcinoma with glycosylphosphatidylinositol-anchored TIMP-1 blocks TGF-β1 activation and reduces regulatory ID gene expression
- Gingipain aminopeptidase activities in Porphyromonas gingivalis
- CLIPPER: an add-on to the Trans-Proteomic Pipeline for the automated analysis of TAILS N-terminomics data
- Review
- Integration of cellular bioenergetics with mitochondrial quality control and autophagy
- Research Articles/Short Communications
- Genes and Nucleic Acids
- A conformational switch is responsible for the reversal of the 6S RNA-dependent RNA polymerase inhibition in Escherichia coli
- Protein Structure and Function
- Molecular determinants of human dipeptidyl peptidase III sensitivity to thiol modifying reagents
- Modular structure of HEL protein from Arabidopsis reveals new potential functions for PR-4 proteins
- Proteolysis
- Characterization of angiotensin I-converting enzyme N-domain selectivity using positional-scanning combinatorial libraries of fluorescence resonance energy transfer peptides
- Mast cells limit extracellular levels of IL-13 via a serglycin proteoglycan-serine protease axis
