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Previously, our group showed an activation of myofibroblasts and matrix remodeling in rat lungs after IUGR. Because growth hormone (GH) and insulin-like growth factor I (IGF-I) regulate development and growth, we queried 1) whether GH\/IGF-I signaling is dysregulated in lungs after IUGR and 2) whether GH\/IGF-I signaling is linked to neonatal lung myofibroblast function. IUGR was induced in Wistar rats by isocaloric low-protein diet during gestation. Lungs were obtained at embryonic day (E) 21, postnatal day (P) 3, P12, and P23. Murine embryonic fibroblasts (MEF) or primary neonatal myofibroblasts from rat lungs of control (pnF<jats:sup>Co<\/jats:sup>) and IUGR (pnF<jats:sup>IUGR<\/jats:sup>) were used for cell culture studies. In the intrauterine phase (E21), we found a reduction in GH receptor (GH-R), Stat5 signaling and IGF-I expression in lungs after IUGR. In the postnatal phase (P3\u2013P23), catchup growth after IUGR was linked to increased GH mRNA, GH-R protein, activation of proliferative Stat5\/Akt signaling, cyclin D1 and PCNA in rat lungs. On P23, a thickening of the alveolar septae was related to increased vimentin and matrix deposition, indicating fibrosis. In cell culture studies, nutrient deprivation blocked GH-R\/IGF-IR signaling and proliferation in MEFs; this was reversed by IGF-I. Proliferation and Stat5 activation were increased in pnF<jats:sup>IUGR<\/jats:sup>. IGF-I and GH induced proliferation and migration of pnF<jats:sup>Co<\/jats:sup>; only IGF-I had these effects on pnF<jats:sup>IUGR<\/jats:sup>. Thus, we show a novel mechanism by which the GH\/IGF-I axis in lung myofibroblasts could account for structural lung changes after IUGR. <\/jats:p>","DOI":"10.1152\/ajplung.00413.2017","type":"journal-article","created":{"date-parts":[[2018,7,26]],"date-time":"2018-07-26T07:34:12Z","timestamp":1532590452000},"page":"L623-L637","source":"Crossref","is-referenced-by-count":13,"title":["Novel functional role of GH\/IGF-I in neonatal lung myofibroblasts and in rat lung growth after intrauterine growth restriction"],"prefix":"10.1152","volume":"315","author":[{"given":"Jawed","family":"Nawabi","sequence":"first","affiliation":[{"name":"Translational Experimental Pediatrics, Experimental Pulmonology, University Hospital for Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Cologne, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Vohlen","sequence":"additional","affiliation":[{"name":"Translational Experimental 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