Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity
| العنوان: | Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity |
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| المؤلفون: | Tim Harrison, Shams-un-nisa Naveed, Dominick E. Shaw, Catherine Reynolds, David A. Jackson, Debbie Clements, Irshad Soomro, Charlotte K. Billington, Sebastian L. Johnston, Simon R. Johnson, Christopher J Philp |
| المصدر: | American Journal of Respiratory and Critical Care Medicine. 195:1000-1009 |
| بيانات النشر: | American Thoracic Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Spirometry, Pathology, medicine.medical_specialty, Myocytes, Smooth Muscle, Cell Culture Techniques, Bronchi, Inflammation, Critical Care and Intensive Care Medicine, Severity of Illness Index, Bronchial Provocation Tests, Extracellular matrix, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Respiratory system, Asthma, medicine.diagnostic_test, business.industry, Muscle, Smooth, respiratory system, medicine.disease, Mast cell, respiratory tract diseases, 3. Good health, 030104 developmental biology, Bronchoalveolar lavage, medicine.anatomical_structure, 030228 respiratory system, Immunology, Female, Bronchoconstriction, Bronchial Hyperreactivity, Matrix Metalloproteinase 1, medicine.symptom, business |
| الوصف: | Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma.To investigate whether MMP-1 could be activated by mast cells and increase asthma severity.Patients with stable asthma and healthy control subjects underwent spirometry, methacholine challenge, and bronchoscopy, and their airway smooth muscle cells were grown in culture. A second asthma group and control subjects had symptom scores, spirometry, and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extracellular matrix was prepared from decellularized airway smooth muscle cultures. MMP-1 protein and activity were assessed.Airway smooth muscle cells generated pro-MMP-1, which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extracellular matrix, which enhanced subsequent airway smooth muscle growth by 1.5-fold (P 0.05), which was dependent on MMP-1 activation. In asthma, airway pro-MMP-1 was 5.4-fold higher than control subjects (P = 0.002). Mast cell numbers were associated with airway smooth muscle proliferation and MMP-1 protein associated with bronchial hyperresponsiveness. During exacerbations, MMP-1 activity increased and was associated with fall in FEVMMP-1 is activated by mast cell tryptase resulting in a proproliferative extracellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, MMP-1 levels are associated with bronchial hyperresponsiveness, and MMP-1 activation are associated with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing MMP activation, airway smooth muscle growth, and airway responsiveness. |
| تدمد: | 1535-4970 1073-449X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9c65f19a14fcb0a399dd0ccf7140b3adTest https://doi.org/10.1164/rccm.201604-0822ocTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9c65f19a14fcb0a399dd0ccf7140b3ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15354970 1073449X |
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