{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T07:40:44Z","timestamp":1779262844425,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":851,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>Airway wall remodelling in asthma is characterised by a number of structural changes, including an increase in the volume of airway smooth muscle (ASM), and the abundance of the extracellular matrix (ECM) protein, collagen, is increased. We have investigated the mechanism of collagen\u2010induced glucocorticoid resistance of proliferation, and migration of ASM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>\n                      ASM cultured from human airways has been seeded on to either type I monomeric collagen or a laminin pentapeptide, YIGSR. The role of \u03b1\n                      <jats:sub>2<\/jats:sub>\n                      \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      integrin in the collagen\u2010induced glucocorticoid resistance was investigated using a function blocking monoclonal antibody.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results:<\/jats:title>\n                    <jats:p>Culture of ASM on collagen I, but not laminin, led to a greater proliferative response that was insensitive to regulation by dexamethasone (100\u2003nM). The anti\u2010migratory effects of the glucocorticoid, fluticasone propionate (1\u2003nM) were also impaired by contact of ASM with collagen. The impaired anti\u2010mitogenic action of dexamethasone was associated with a failure to reduce the levels of the rate\u2010limiting cell cycle regulatory protein, cyclin D1. When signalling through the \u03b12\u03b21 integrin was reduced, dexamethasone\u2010mediated reductions in proliferation and cyclin D1 levels were restored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications:<\/jats:title>\n                    <jats:p>In the collagen\u2010rich microenvironment of the inflamed and fibrotic asthmatic airway, integrin\/ECM interactions may contribute to glucocorticoid resistance.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2006)\n                      <jats:bold>149<\/jats:bold>\n                      , 365\u2013373. doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706881\">10.1038\/sj.bjp.0706881<\/jats:ext-link>\n                    <\/jats:p>\n                  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