{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:22:11Z","timestamp":1770834131039,"version":"3.50.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cystic fibrosis (CF) is a lethal genetic disease characterized by progressive lung damage and airway obstruction. The majority of patients demonstrate airway hyperresponsiveness (AHR), which is associated with more rapid lung function decline. Recent studies in the neonatal CF pig demonstrated airway smooth muscle (ASM) dysfunction. These findings, combined with observed CF transmembrane conductance regulator (CFTR) expression in ASM, suggest that a fundamental defect in ASM function contributes to lung function decline in CF. One established driver of AHR and ASM dysfunction is transforming growth factor (TGF) \u03b21, a genetic modifier of CF lung disease. Prior studies demonstrated that TGF\u03b2 exposure in CF mice drives features of CF lung disease, including goblet cell hyperplasia and abnormal lung mechanics. CF mice displayed aberrant responses to pulmonary TGF\u03b2, with elevated PI3K signaling and greater increases in lung resistance compared with controls. Here, we show that TGF\u03b2 drives abnormalities in CF ASM structure and function through PI3K signaling that is enhanced in CFTR-deficient lungs. CF and non-CF mice were exposed intratracheally to an adenoviral vector containing the TGF\u03b21 cDNA, empty vector, or PBS only. We assessed methacholine-induced AHR, bronchodilator response, and ASM area in control and CF mice. Notably, CF mice demonstrated enhanced AHR and bronchodilator response with greater ASM area increases compared with non-CF mice. Furthermore, therapeutic inhibition of PI3K signaling mitigated the TGF\u03b2-induced AHR and goblet cell hyperplasia in CF mice. These results highlight a latent AHR phenotype in CFTR deficiency that is enhanced through TGF\u03b2-induced PI3K signaling.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0158oc","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T15:39:51Z","timestamp":1578670791000},"page":"657-667","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":9,"title":["Subacute TGF\u03b2 Exposure Drives Airway Hyperresponsiveness in Cystic Fibrosis Mice through the PI3K Pathway"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3278-2161","authenticated-orcid":false,"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 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satish 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