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Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis

Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis
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 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).
tuberculosis, cathepsin K, rabbit, collagen, collagenolysis, RNAseq
0022-1899
618-627
Kubler, A.
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Larsson, C.
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Luna, B.
90970267-4cff-4558-9717-e31c4ea6f298
Andrade, B.B.
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Amaral, E.P.
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Urbanowski, M.
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Orandle, M.
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Block, K.
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Ammerman, N.C.
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Cheung, L.S.
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Winglee, K.
fb74fef3-9165-49b2-b093-eac5bcf3ad3c
Halushka, M.
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Park, J.K.
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Sher, A.
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Friedland, J.S.
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Elkington, P.T.
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Bishai, W.R.
adcbabf1-0ec4-408e-b538-0998da585ce2
Kubler, A.
4ffda2c6-0a9a-4356-b4d0-1066b6297147
Larsson, C.
68c26533-ae1c-4258-bc79-ed0614a2f9e1
Luna, B.
90970267-4cff-4558-9717-e31c4ea6f298
Andrade, B.B.
e8a0a8cc-d98a-4f6d-9c02-9d5040a267f5
Amaral, E.P.
56d14032-47ca-4c66-8a3a-2f2e62271e9c
Urbanowski, M.
aa07f4d6-4117-4827-abaf-58b8f06f84b1
Orandle, M.
6f6d9a8c-ed9f-4c4e-83c9-b2f999f0d3d6
Block, K.
14b7ed70-c498-4e38-bf5c-e00cfe0f6e3f
Ammerman, N.C.
fd64ece2-5366-4e44-923a-9f272485f698
Cheung, L.S.
a3728136-8485-4f95-b52f-110618f5b8c1
Winglee, K.
fb74fef3-9165-49b2-b093-eac5bcf3ad3c
Halushka, M.
54129019-5841-4806-ad91-0ab51f1c61d0
Park, J.K.
5e8424b4-af89-44b3-a6ef-9318549368d7
Sher, A.
c148fa25-f000-48bd-845b-eae9af0a3979
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Bishai, W.R.
adcbabf1-0ec4-408e-b538-0998da585ce2

Kubler, A., Larsson, C., Luna, B., Andrade, B.B., Amaral, E.P., Urbanowski, M., Orandle, M., Block, K., Ammerman, N.C., Cheung, L.S., Winglee, K., Halushka, M., Park, J.K., Sher, A., Friedland, J.S., Elkington, P.T. and Bishai, W.R. (2016) Cathepsin K contributes to cavitation and collagen turnover in pulmonary tuberculosis. The Journal of Infectious Diseases, 213 (4), 618-627. (doi:10.1093/infdis/jiv458). (PMID:26416658)

Record type: Article

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).

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More information

Accepted/In Press date: 31 August 2015
e-pub ahead of print date: 27 September 2015
Published date: 15 February 2016
Keywords: tuberculosis, cathepsin K, rabbit, collagen, collagenolysis, RNAseq
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 382252
URI: https://eprints.soton.ac.uk/id/eprint/382252
ISSN: 0022-1899
PURE UUID: 0460f720-95d8-4a17-9851-e0e15951ae4e
ORCID for P.T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 27 Oct 2015 14:49
Last modified: 10 Dec 2019 01:37

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Contributors

Author: A. Kubler
Author: C. Larsson
Author: B. Luna
Author: B.B. Andrade
Author: E.P. Amaral
Author: M. Urbanowski
Author: M. Orandle
Author: K. Block
Author: N.C. Ammerman
Author: L.S. Cheung
Author: K. Winglee
Author: M. Halushka
Author: J.K. Park
Author: A. Sher
Author: J.S. Friedland
Author: P.T. Elkington ORCID iD
Author: W.R. Bishai

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