Novel functional role of GH/IGF1 in neonatal lung myofibroblasts and in rat lung growth after intrauterine growth restriction

Intrauterine growth restriction (IUGR) is a risk factor for neonatal chronic lung disease (CLD), characterized by reduced alveoli and fibrosis. Our group showed previously an activation of myofibroblasts and matrix-remodeling in rat lungs after IUGR. Since Growth Hormone (GH) and Insulin-like growth factor 1 (IGF1) regulate development and growth, we queried (1) if GH/IGF1 signaling is dysregulated in lungs after IUGR; and (2) if GH/IGF1 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 (pnFCo) and IUGR (pnFIUGR) were used for cell culture studies. Intrauterine phase (E21): we found a reduction of GH-receptor (GH-R), Stat5 signaling and IGF1 expression in lungs after IUGR. Postnatal phase (P3-P23): catch-up growth after IUGR was linked to incr...