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The histopathology of BPD is characterized by an arrest of alveolarization with fibroblast activation. The Wnt\/\u03b2-catenin signaling pathway is important in early lung development. When Wnt signaling is active, phosphorylation of \u03b2-catenin by tyrosine kinases at activating sites, specifically at tyrosine 489 (Y489), correlates with nuclear localization of \u03b2-catenin. We examined fetal lung tissue, lung tissue from term newborns, and lung tissue from infants who died with BPD; we found nuclear \u03b2-catenin phosphorylation at Y489 in epithelial and mesenchymal cells in fetal tissue and BPD tissue, but not in the lungs of term infants. Using a 3D human organoid model, we found increased nuclear localization of \u03b2-catenin phosphorylated at Y489 (p-\u03b2-catenin<jats:sup>Y489<\/jats:sup>) after exposure to alternating hypoxia and hyperoxia compared with organoids cultured in normoxia. Exogenous stimulation of the canonical Wnt pathway in organoids was sufficient to cause nuclear localization of p-\u03b2-catenin<jats:sup>Y489<\/jats:sup> in normoxia and mimicked the pattern of \u03b1-smooth muscle actin (\u03b1-SMA) expression seen with fibroblastic activation from oxidative stress. Treatment of organoids with a tyrosine kinase inhibitor prior to cyclic hypoxia-hyperoxia inhibited nuclear localization of p-\u03b2-catenin<jats:sup>Y489<\/jats:sup> and prevented \u03b1-SMA expression by fibroblasts. Posttranslational phosphorylation of \u03b2-catenin is a transient feature of normal lung development. Moreover, the persistence of p-\u03b2-catenin<jats:sup>Y489<\/jats:sup> is a durable marker of fibroblast activation in BPD and may play an important role in BPD disease pathobiology. <\/jats:p>","DOI":"10.1152\/ajplung.00477.2016","type":"journal-article","created":{"date-parts":[[2016,12,9]],"date-time":"2016-12-09T22:56:42Z","timestamp":1481324202000},"page":"L186-L195","source":"Crossref","is-referenced-by-count":39,"title":["Posttranslational modification of \u03b2-catenin is associated with pathogenic fibroblastic changes in bronchopulmonary dysplasia"],"prefix":"10.1152","volume":"312","author":[{"given":"Jennifer M. 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