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Transforming growth factor-\u03b2 (TGF\u03b2) is the best described genetic modifier of the CF phenotype, but its mechanism of action is unknown. We hypothesized that TGF\u03b2 is sufficient to drive pathognomonic features of CF lung disease in vivo and that CFTR deficiency enhances susceptibility to pathological TGF\u03b2 effects. A CF mouse model and littermate controls were exposed intratracheally to an adenoviral vector containing the TGF\u03b21 cDNA (Ad-TGF\u03b2), empty vector, or PBS only. Studies were performed 1 wk after treatment, including lung mechanics, collection of bronchoalveolar lavage fluid, and analysis of lung histology, RNA, and protein. CF and non-CF mice showed similar weight loss, inflammation, goblet cell hyperplasia, and Smad pathway activation after Ad-TGF\u03b2 treatment. Ad-TGF\u03b2 produced greater abnormalities in lung mechanics in CF versus control mice, which was uniquely associated with induction of phosphoinositide 3-kinase and mitogen-activated protein kinase signaling. CFTR transcripts were reduced, and epithelial sodium channel transcripts were increased in CF and non-CF mice, whereas the goblet cell transcription factors, forkhead ortholog A3 and SAM-pointed domain-containing ETS-like factor, were increased in non-CF but not CF mice following Ad-TGF\u03b2 treatment. Pulmonary TGF\u03b21 expression was sufficient to produce pulmonary remodeling and abnormalities in lung mechanics that were associated with both shared and unique cell signaling pathway activation in CF and non-CF mice. These results highlight the multifunctional impact of TGF\u03b2 on pulmonary pathology in vivo and identify cellular-response differences that may impact CF lung pathology.<\/jats:p>","DOI":"10.1152\/ajplung.00530.2017","type":"journal-article","created":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T11:49:51Z","timestamp":1528372191000},"page":"L456-L465","source":"Crossref","is-referenced-by-count":12,"title":["Subacute TGF\u03b2 expression drives inflammation, goblet cell hyperplasia, and pulmonary function abnormalities in mice with effects dependent on CFTR function"],"prefix":"10.1152","volume":"315","author":[{"given":"Elizabeth L.","family":"Kramer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio"},{"name":"Division of Pulmonary Medicine, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William 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