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We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-\u03b2 pathway, a key player in lung development and repair. Pulmonary expression of TGF-\u03b2 signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-\u03b2\/Smad2\/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-\u03b2 transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2\/3 activation. After TO, subtle accumulation of collagen and \u03b1-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-\u03b2\/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.<\/jats:p>","DOI":"10.1152\/ajplung.00122.2015","type":"journal-article","created":{"date-parts":[[2015,12,5]],"date-time":"2015-12-05T04:50:50Z","timestamp":1449291050000},"page":"L311-L327","source":"Crossref","is-referenced-by-count":17,"title":["Increased TGF-\u03b2: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?"],"prefix":"10.1152","volume":"310","author":[{"given":"Aline","family":"Vuckovic","sequence":"first","affiliation":[{"name":"Laboratory of Physiology and Pathophysiology, Faculty of Medicine, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Herber-Jonat","sequence":"additional","affiliation":[{"name":"Division of Neonatology, University Children's Hospital, Perinatal Center, Ludwig-Maximilian-University Munich, Munich, 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