Am. J. Respir. Cell Mol. Biol., Vol 16, No. 5, 05 1997, 538-548.
Re-emergence of a fetal pattern of insulin-like growth factor expression during hyperoxic rat lung injury
KA Veness-Meehan, BM Moats-Staats, WA Price and AD Stiles
Department of Pediatrics, University of North Carolina at Chapel Hill, 27599-7596, USA.
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.
