Re-emergence of a fetal pattern of insulin-like growth factor expression during hyperoxic rat lung injury.
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.
Veness-Meehan
K A
KA
Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7596, USA.
Moats-Staats
B M
BM
Price
W A
WA
Stiles
A D
AD
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
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D010100:Oxygen