{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:44:19Z","timestamp":1790318659102,"version":"4.1.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Matrix metalloproteinase-1 (MMP-1) and mast cells are present in the airways of people with asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate whether MMP-1 could be activated by mast cells and increase asthma severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Airway smooth muscle cells generated pro\u2013MMP-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\u2009&amp;lt;\u20090.05), which was dependent on MMP-1 activation. In asthma, airway pro\u2013MMP-1 was 5.4-fold higher than control subjects (P\u2009=\u20090.002). 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 FEV1 and worsening asthma symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MMP-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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201604-0822oc","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T09:04:03Z","timestamp":1488791043000},"page":"1000-1009","source":"Crossref","is-referenced-by-count":63,"title":["Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity"],"prefix":"10.1093","volume":"195","author":[{"given":"Shams-un-nisa","family":"Naveed","sequence":"first","affiliation":[{"name":"Division of Respiratory Medicine and Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Clements","sequence":"additional","affiliation":[{"name":"Division of Respiratory 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