MMP-1 activation contributes to airway smooth muscle growth and asthma severity
Introduction: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy controls underwent spirometry, met...
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| Format: | Article |
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American Thoracic Society
2017
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| Online Access: | https://eprints.nottingham.ac.uk/40029/ |
| _version_ | 1848795971020914688 |
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| author | Naveed, Shams-un-nisa Clements, Debbie Jackson, David J. Philp, Christopher Billington, Charlotte K. Soomro, Irshad N. Reynolds, Catherine Harrison, Timothy W. Johnston, Sebastian L. Shaw, Dominick E. Johnson, Simon R. |
| author_facet | Naveed, Shams-un-nisa Clements, Debbie Jackson, David J. Philp, Christopher Billington, Charlotte K. Soomro, Irshad N. Reynolds, Catherine Harrison, Timothy W. Johnston, Sebastian L. Shaw, Dominick E. Johnson, Simon R. |
| author_sort | Naveed, Shams-un-nisa |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Introduction: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy controls underwent spirometry, methacholine challenge, bronchoscopy and their airway smooth muscle cells were grown in culture. A second asthma group and controls had symptom scores, spirometry and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extra-cellular matrix was prepared from decellularised airway smooth muscle cultures. Matrix metalloproteinase-1 protein and activity were assessed. Results: Airway smooth muscle cells generated pro-matrix metalloproteinase-1 which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extra-cellular matrix which enhanced subsequent airway smooth muscle growth by 1.5 fold (p<0.05) which was dependent on matrix metalloproteinase-1 activation. In asthma, airway pro-matrix metalloproteinase-1 was 5.4 fold higher than control subjects (p=0.002). Mast cell numbers were associated with airway smooth muscle proliferation and matrix metalloproteinase-1 protein associated with bronchial hyper-responsiveness. During exacerbations, matrix metalloproteinase-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: Matrix metalloproteinase-1 is activated by mast cell tryptase resulting in a pro-proliferative extra-cellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, matrix metalloproteinase-1 levels are associated with bronchial hyper-responsiveness and matrix metalloproteinase-1 activation with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing matrix metalloproteinase activation, airway smooth muscle growth and airway responsiveness. |
| first_indexed | 2025-11-14T19:40:33Z |
| format | Article |
| id | nottingham-40029 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:40:33Z |
| publishDate | 2017 |
| publisher | American Thoracic Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-400292024-08-15T15:22:25Z https://eprints.nottingham.ac.uk/40029/ MMP-1 activation contributes to airway smooth muscle growth and asthma severity Naveed, Shams-un-nisa Clements, Debbie Jackson, David J. Philp, Christopher Billington, Charlotte K. Soomro, Irshad N. Reynolds, Catherine Harrison, Timothy W. Johnston, Sebastian L. Shaw, Dominick E. Johnson, Simon R. Introduction: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. Methods: Patients with stable asthma and healthy controls underwent spirometry, methacholine challenge, bronchoscopy and their airway smooth muscle cells were grown in culture. A second asthma group and controls had symptom scores, spirometry and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extra-cellular matrix was prepared from decellularised airway smooth muscle cultures. Matrix metalloproteinase-1 protein and activity were assessed. Results: Airway smooth muscle cells generated pro-matrix metalloproteinase-1 which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extra-cellular matrix which enhanced subsequent airway smooth muscle growth by 1.5 fold (p<0.05) which was dependent on matrix metalloproteinase-1 activation. In asthma, airway pro-matrix metalloproteinase-1 was 5.4 fold higher than control subjects (p=0.002). Mast cell numbers were associated with airway smooth muscle proliferation and matrix metalloproteinase-1 protein associated with bronchial hyper-responsiveness. During exacerbations, matrix metalloproteinase-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. Conclusions: Matrix metalloproteinase-1 is activated by mast cell tryptase resulting in a pro-proliferative extra-cellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, matrix metalloproteinase-1 levels are associated with bronchial hyper-responsiveness and matrix metalloproteinase-1 activation with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing matrix metalloproteinase activation, airway smooth muscle growth and airway responsiveness. American Thoracic Society 2017-04-15 Article PeerReviewed Naveed, Shams-un-nisa, Clements, Debbie, Jackson, David J., Philp, Christopher, Billington, Charlotte K., Soomro, Irshad N., Reynolds, Catherine, Harrison, Timothy W., Johnston, Sebastian L., Shaw, Dominick E. and Johnson, Simon R. (2017) MMP-1 activation contributes to airway smooth muscle growth and asthma severity. American Journal of Respiratory and Critical Care Medicine, 195 (8). pp. 1000-1009. ISSN 1535-4970 Asthma Extracellular matrix Airway remodeling Airway smooth muscle Mast cells http://www.atsjournals.org/doi/abs/10.1164/rccm.201604-0822OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed doi:10.1164/rccm.201604-0822OC doi:10.1164/rccm.201604-0822OC |
| spellingShingle | Asthma Extracellular matrix Airway remodeling Airway smooth muscle Mast cells Naveed, Shams-un-nisa Clements, Debbie Jackson, David J. Philp, Christopher Billington, Charlotte K. Soomro, Irshad N. Reynolds, Catherine Harrison, Timothy W. Johnston, Sebastian L. Shaw, Dominick E. Johnson, Simon R. MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title_full | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title_fullStr | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title_full_unstemmed | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title_short | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
| title_sort | mmp-1 activation contributes to airway smooth muscle growth and asthma severity |
| topic | Asthma Extracellular matrix Airway remodeling Airway smooth muscle Mast cells |
| url | https://eprints.nottingham.ac.uk/40029/ https://eprints.nottingham.ac.uk/40029/ https://eprints.nottingham.ac.uk/40029/ |