Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen.
Exposure of neonatal rats to > or = 95% O2 for 2 wk, a widely used model of oxidant/antioxidant interactions in neonatal lung injury, results in arrested lung growth without the dysplastic lesions observed in chronic human neonatal lung injury. To determine whether dysplastic lung cell growth would be seen at lesser O2 concentrations, we exposed newborn rats to either 95% O2 for 1 wk followed by 60% O2 for 1 wk, or to 60% O2 for 2 wk. Exposure to 95% O2 for 1 wk profoundly inhibited lung DNA synthesis. Recovery of synthesis did not occur during the 2nd wk in 60% O2, nor were areas of dysplastic growth evident in lung tissue. In contrast, a continuous 2-wk exposure to 60% O2 resulted in a slight increase in lung weight with a significant reduction in lung volume over a range of inflation pressures. Also seen was an overall, but inhomogeneous, reduction in lung cell DNA synthesis. A preliminary analysis of affected cell types suggested that inhibition of DNA synthesis affected endothelial cells more than interstitial cells, whereas DNA synthesis increased in type II pneumocytes. Areas of reduced DNA synthesis were interspersed with patchy areas of parenchymal thickening and active DNA synthesis. These areas of parenchymal thickening, but not other areas, had increased immunoreactive IGF-I and the type I IGF receptor. These data are consistent with a direct effect of O2 on growth factor and growth factor receptor expression in causing dysplastic lung cell growth in chronic neonatal lung injury.
Han
R N
RN
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Buch
S
S
Tseu
I
I
Young
J
J
Christie
N A
NA
Frndova
H
H
Lye
S J
SJ
Post
M
M
Tanswell
A K
AK
D000818:Animals; D000831:Animals, Newborn; D002374:Catalase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D015870:Gene Expression; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004247:DNA; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D017526:Receptor, IGF Type 1; D010100:Oxygen