@article{1e70dbe613904e55a121a827d7ba7e57,
title = "Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis",
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).",
keywords = "RNAseq, cathepsin K, collagen, collagenolysis, rabbit, tuberculosis",
author = "Andre Kubler and Christer Larsson and Brian Luna and Andrade, {Bruno B.} and Amaral, {Eduardo P.} and Michael Urbanowski and Marlene Orandle and Kevin Bock and Ammerman, {Nicole C.} and Cheung, {Laurene S.} and Kathryn Winglee and Marc Halushka and Park, {Jin Kyun} and Alan Sher and Friedland, {Jon S.} and Elkington, {Paul T.} and Bishai, {William R.}",
note = "Funding Information: We thank Dr Irini Sereti (NIAID, NIH) for providing the serum samples from patients with tuberculosis. A. K., B. L., C. L., N. C. A., L. S. C., and K.W. designed and performed the animal experiments. A. K., B. L., C. L., M. U., and K. W. designed and conducted RNA analysis. B. B. A., M. O., K. B., M. H., and J. K. P. developed, designed, performed, and interpreted the histopathological assessment of rabbit and human tissues. E. P. A. and B. B. A. designed and performed human serum collection and analysis. A. S., J. S. F., P. T. E., and W. R. B. contributed to study design, manuscript preparation, and grant acquisition. All authors reviewed and contributed to manuscript preparation. This work was supported by the Howard Hughes Medical Institute (to W. R. B.), the National Institutes of Health (NIH; R01 AI 079590, R01 AI037856, and R01 AI036973 to W. R. B. and R33 A1102239 to P. E.), the NIH Intramural Research Program (to A. S., B. B. A., and E. P. A.), Imperial College London (to A. K. and J. S. F.), the Swedish Research Council (to C. L.), and the Swedish Society for Medical Research (to C. L.). Publisher Copyright: {\textcopyright} The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.",
year = "2016",
month = feb,
day = "15",
doi = "10.1093/infdis/jiv458",
language = "English (US)",
volume = "213",
pages = "618--627",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "4",
}