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- Title
Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis.
- Authors
Kubler, Andre; Larsson, Christer; Luna, Brian; Andrade, Bruno B.; Amaral, Eduardo P.; Urbanowski, Michael; Orandle, Marlene; Bock, Kevin; Ammerman, Nicole C.; Cheung, Laurene S.; Winglee, Kathryn; Halushka, Marc; Jin Kyun Park; Sher, Alan; Friedland, Jon S.; Elkington, Paul T.; Bishai, William R.; Park, Jin Kyun
- Abstract
Cavitation in tuberculosis enables highly efficient person-to-person aerosol transmission. We performed transcriptomics in the rabbit cavitary tuberculosis model. Among 17 318 transcripts, we identified 22 upregulated proteases. Five type I collagenases were overrepresented: cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase 1 (MMP-1), MMP-13, and MMP-14. Studies of collagen turnover markers, specifically, collagen type I C-terminal propeptide (CICP), urinary deoxypyridinoline (DPD), and urinary helical peptide, revealed that cavitation in tuberculosis leads to both type I collagen destruction and synthesis and that proteases other than MMP-1, MMP-13, and MMP-14 are involved, suggesting a key role for CTSK. We confirmed the importance of CTSK upregulation in human lung specimens, using immunohistochemical analysis, which revealed perigranulomatous staining for CTSK, and we showed that CTSK levels were increased in the serum of patients with tuberculosis, compared with those in controls (3.3 vs 0.3 ng/mL; P = .005).
- Subjects
CATHEPSINS; CAVITATION; TUBERCULOSIS; PROTEOLYTIC enzymes; COLLAGEN; ANIMAL experimentation; BIOLOGICAL models; IMMUNOHISTOCHEMISTRY; LUNGS; RABBITS; GENE expression profiling; METABOLISM
- Publication
Journal of Infectious Diseases, 2016, Vol 213, Issue 4, p618
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiv458