REEMERGENCE 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 an d characteristic architectural changes. It is likely that growth facto rs produced and acting locally are important to these precesses. Insul in-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 in jury are suggested by their expression during lung development and by studies showing changes in IGF-I expression by activated alveolar macr ophages, and increases in IGF-II peptide in oxidant arrested alveolar epithelial cells. To investigate whether the expression of IGF-I and I GF-II are changed with hyperoxic exposure, newborn rats were exposed t o 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 hypero xia. In situ hybridization histochemistry and immunohistochemical stai ning demonstrated spatial patterns of IGF-I and IGF-II expression simi lar 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 lun g injury resident lung cells may re-express IGFs in a manner reminisce nt of fetal development, and activated inflammatory cells may contribu te to the proliferative response through autocrine and paracrine mecha nisms.