{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:25:58Z","timestamp":1791159958460,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":[[2006,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although smooth muscle hypertrophy is present in asthmatic airways, little is known about the biochemical pathways regulating airway smooth muscle protein synthesis, cell size, or accumulation of contractile apparatus proteins. We sought to develop a model of airway smooth muscle hypertrophy in primary cells using a physiologically relevant stimulus. We hypothesized that transforming growth factor (TGF)-\u03b2 induces hypertrophy in primary bronchial smooth muscle cells. Primary human bronchial smooth muscle cells isolated from unacceptable lung donor tissue were studied. Cells were seeded on uncoated plastic dishes at 50% confluence and TGF-\u03b2 was added. Experiments were performed in the absence of serum. TGF-\u03b2 increased cell size and total protein synthesis, expression of \u03b1-smooth muscle actin and smooth muscle myosin heavy chain, formation of actomyosin filaments, and cell shortening to acetylcholine. Further, TGF-\u03b2 increased airway smooth muscle \u03b1-actin synthesis in the presence of the transcriptional inhibitor actinomycin D, evidence that translational control is a physiologically important element of the observed hypertrophy. TGF-\u03b2 induced the phosphorylation of eukaryotic translation initiation factor-4E\u2013binding protein, a signaling event specifically involved in translational control. Finally, two inhibitors of 4E-binding protein phosphorylation, the phosphoinositol 3-kinase inhibitor LY294002 and a phosphorylation site mutant of 4E-binding protein-1 that dominantly inhibits eukaryotic initiation factor-4E, each blocked TGF-\u03b2\u2013 induced \u03b1-actin expression and cell enlargement. We conclude that TGF-\u03b2 induces hypertrophy of primary bronchial smooth muscle cells. Further, phosphorylation of 4E-binding protein is required for the observed hypertrophy.<\/jats:p>","DOI":"10.1165\/rcmb.2005-0166oc","type":"journal-article","created":{"date-parts":[[2005,10,26]],"date-time":"2005-10-26T03:43:46Z","timestamp":1130298226000},"page":"247-254","source":"Crossref","is-referenced-by-count":89,"title":["Transforming Growth Factor-\u03b2 Induces Airway Smooth Muscle Hypertrophy"],"prefix":"10.1093","volume":"34","author":[{"given":"Adam M.","family":"Goldsmith","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Kelley","family":"Bentley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil N.","family":"Bitar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane C.","family":"Fingar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of Cell and Developmental Biology, and Department of Medicine, University of Michigan, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc B.","family":"Hershenson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Communicable Diseases, Department of Molecular and Integrative Physiology, Department of 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