title: Re-emergence of a fetal pattern of insulin-like growth factor expression during hyperoxic rat lung injury.
abstract: Chronic injury to the developing lung results in cell proliferation and characteristic architectural changes. It is likely that growth factors produced and acting locally are important to these processes. Insulin-like growth factors I and II (IGF-I and IGF-II) are peptide growth factors expressed by lung cells. Roles for IGF-I and IGF-II in lung injury are suggested by their expression during lung development and by studies showing changes in IGF-I expression by activated alveolar macrophages, and increases in IGF-II peptide in oxidant arrested alveolar epithelial cells. To investigate whether the expression of IGF-I and IGF-II are changed with hyperoxic exposure, newborn rats were exposed to 80-90% oxygen for up to 6 wk and Northern hybridization analyses, in situ hybridization histochemistry, immunohistochemical staining, and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed. Northern hybridization analyses of RNA extracted from whole lung showed increases in IGF-I and IGF-II mRNAs with prolonged hyperoxia. In situ hybridization histochemistry and immunohistochemical staining demonstrated spatial patterns of IGF-I and IGF-II expression similar to those seen during fetal lung development. In addition, alveolar macrophages express IGF-I and type II epithelial cells express IGF-II in control and oxygen-injured lung. These results suggest that in lung injury resident lung cells may re-express IGFs in a manner reminiscent of fetal development, and activated inflammatory cells may contribute to the proliferative response through autocrine and paracrine mechanisms.
authors.affiliation: Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7596, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Veness-Meehan
authors.forename: B M
authors.initials: BM
authors.lastname: Moats-Staats
authors.forename: W A
authors.initials: WA
authors.lastname: Price
authors.forename: A D
authors.initials: AD
authors.lastname: Stiles
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D016676:Macrophages, Alveolar / Q000737:chemistry; D009130:Muscle, Smooth / Q000737:chemistry; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010100:Oxygen