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).
Original language | English (US) |
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Pages (from-to) | 618-627 |
Number of pages | 10 |
Journal | Journal of Infectious Diseases |
Volume | 213 |
Issue number | 4 |
DOIs | |
State | Published - Feb 15 2016 |
Keywords
- RNAseq
- cathepsin K
- collagen
- collagenolysis
- rabbit
- tuberculosis
ASJC Scopus subject areas
- General Medicine