Regulation of the epidermal growth factor receptor in fetal rat lung fibroblasts during late gestation.
Lung epithelial cell differentiation is predominantly regulated by mesenchymal-epithelial cell communication. We have previously shown that epidermal growth factor (EGF) positively influences this process, and that EGF receptor (EGF-R) binding in fetal rat lung fibroblasts peaks on d18-19 of gestation, just before the onset of augmented surfactant synthesis. This regulation of EGF-R in late gestation fetal lung fibroblasts may control the timing of mesenchymal-epithelial cell communication leading to surfactant synthesis. Hormones and growth factors exert positive and negative influences on lung development, but whether they regulate the EGF-R is unknown. We hypothesized that positive [EGF, cortisol, retinoic acid (RA)] and negative [transforming growth-factor-beta1 (TGF-beta1), dihydrotestosterone (DHT)] regulators of lung cell development regulate the EGF-R in the fetal lung. We studied EGF-R binding and protein abundance in sex-specific fetal rat lung fibroblasts cultured at d17, d19, and d21. EGF-R binding was significantly elevated after RA (both sexes d17 and d19, females d21) and after DHT (females d19) treatment. EGF and cortisol had minimal or inhibitory effects on EGF-R binding. Western blot analysis showed that the observed changes in EGF-R binding were associated with similar changes in EGF-R protein. We conclude that factors that affect lung maturation continue to regulate EGF-R in a developmental, sex-specific manner during late gestation.
Dammann
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Division of Newborn Medicine, The Floating Hospital for Children, New England Medical Center, Tufts University, Boston, Massachusetts 02111, USA. christiane.dammann@es.nemc.org
Nielsen
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D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005865:Gestational Age; D006854:Hydrocortisone / Q000494:pharmacology; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014212:Tretinoin / Q000494:pharmacology
D013196:Dihydrotestosterone; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D006854:Hydrocortisone