Cathepsin K Contributes to Cavitation and Collagen Turnover in Pulmonary Tuberculosis

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...

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Bibliographic Details
Published in:The Journal of infectious diseases 2016-02, Vol.213 (4), p.618-627
Main 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, Park, Jin Kyun, Sher, Alan, Friedland, Jon S., Elkington, Paul T., Bishai, William R.
Format: Article
Language:English
Subjects:
Animals
cathepsin K
Cathepsin K - metabolism
collagen
Collagen - metabolism
Collagenases - metabolism
collagenolysis
Disease Models, Animal
Female
Gene Expression Profiling
Immunohistochemistry
Lung - pathology
Major and Brief Reports
Mycobacterium
PATHOGENESIS AND HOST RESPONSE
rabbit
Rabbits
RNAseq
tuberculosis
Tuberculosis, Pulmonary - pathology
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Summary: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).
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiv458