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Our group found that integrin \u03b24 (ITGB4) is downregulated in the airway epithelium of asthma patients. Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP\u2010rtTA, Tet\u2010O\u2010Cre and ITGB4<jats:sup>f\/f<\/jats:sup> triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the \u03b24<jats:sup>ccsp.cre<\/jats:sup> group appear to be sparse, shortened and lodging. Lung\u2010development\u2010relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis\u2010regulating\u2010relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho\u2010FAK, phospho\u2010GSK3\u03b2 and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3\u03b2 agonist (wortmannin). Airway branching defect of \u03b24<jats:sup>ccsp.cre<\/jats:sup> mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial\u2010specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK\/GSK3\u03b2\/SOX2 signal pathway.<\/jats:p>","DOI":"10.1111\/jcmm.17948","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T09:00:46Z","timestamp":1694509246000},"page":"3760-3772","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Conditional knockout of <scp>ITGB4<\/scp> in bronchial epithelial cells directs bronchopulmonary dysplasia"],"prefix":"10.1111","volume":"27","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Basic Medicine Central South University  Changsha China"},{"name":"Department of Medical Laboratory, School of Medicine Hunan Normal University  Changsha 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