Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis

Andre Kubler; Christer Larsson; Brian Luna; Bruno B. Andrade; Eduardo P. Amaral; Michael Urbanowski; Marlene Orandle; Kevin Bock; Nicole C. Ammerman; Laurene S. Cheung; Kathryn Winglee; Marc Halushka; Jin Kyun Park; Alan Sher; Jon S. Friedland; Paul T. Elkington; William R. Bishai

doi:10.1093/infdis/jiv458

Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis

Andre Kubler, Christer Larsson, Brian Luna, Bruno B. Andrade, Eduardo P. Amaral, Michael Urbanowski, Marlene Orandle, Kevin Bock, Nicole C. Ammerman, Laurene S. Cheung, Kathryn Winglee, Marc Halushka, Jin Kyun Park, Alan Sher, Jon S. Friedland, Paul T. Elkington, William R. Bishai

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

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)
Pages (from-to)	618-627
Number of pages	10
Journal	Journal of Infectious Diseases
Volume	213
Issue number	4
DOIs	https://doi.org/10.1093/infdis/jiv458
State	Published - Feb 15 2016

Keywords

RNAseq
cathepsin K
collagen
collagenolysis
rabbit
tuberculosis

ASJC Scopus subject areas

General Medicine

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10.1093/infdis/jiv458

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Kubler, A., Larsson, C., Luna, B., Andrade, B. B., Amaral, E. P., Urbanowski, M., Orandle, M., Bock, K., Ammerman, N. C., Cheung, L. S., Winglee, K., Halushka, M., Park, J. K., Sher, A., Friedland, J. S., Elkington, P. T., & Bishai, W. R. (2016). Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis. Journal of Infectious Diseases, 213(4), 618-627. https://doi.org/10.1093/infdis/jiv458

Kubler, A, Larsson, C, Luna, B, Andrade, BB, Amaral, EP, Urbanowski, M, Orandle, M, Bock, K, Ammerman, NC, Cheung, LS, Winglee, K, Halushka, M, Park, JK, Sher, A, Friedland, JS, Elkington, PT & Bishai, WR 2016, 'Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis', Journal of Infectious Diseases, vol. 213, no. 4, pp. 618-627. https://doi.org/10.1093/infdis/jiv458

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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.}",

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AU - Kubler, Andre

AU - Larsson, Christer

AU - Luna, Brian

AU - Andrade, Bruno B.

AU - Amaral, Eduardo P.

AU - Urbanowski, Michael

AU - Orandle, Marlene

AU - Bock, Kevin

AU - Ammerman, Nicole C.

AU - Cheung, Laurene S.

AU - Winglee, Kathryn

AU - Halushka, Marc

AU - Park, Jin Kyun

AU - Sher, Alan

AU - Friedland, Jon S.

AU - Elkington, Paul T.

AU - Bishai, William R.

PY - 2016/2/15

Y1 - 2016/2/15

N2 - 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).

AB - 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).

KW - RNAseq

KW - cathepsin K

KW - collagen

KW - collagenolysis

KW - rabbit

KW - tuberculosis

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Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis

Abstract

Keywords

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