Changes in gene expression in hyperoxia-induced neonatal lung injury.
Exposure to high concentrations of oxygen (hyperoxia) can result in lung injury. The biochemical basis of this injury is poorly understood, but it is likely to include alterations in gene expression. Hyperoxia-induced (H-I) cDNAs have been molecularly cloned (Horowitz et al. J. Biol. Chem. 264: 7092-7095, 1989) from the lungs of an adult rabbit exposed to toxic levels of oxygen. One of them (H-I 1) was identified as encoding the tissue inhibitor of metalloproteinases (TIMP), a key regulatory protein of extracellular matrix turnover. Here we identify another clone (H-I 3) as encoding pulmonary surfactant apoprotein A (SP-A). We also show that in neonatal rabbits exposed to 100% oxygen for 96 h, the mRNAs corresponding to TIMP, SP-A, and another H-I gene are increased. These studies have begun to explore specific changes in gene expression associated with neonatal hyperoxic lung injury.
Horowitz
S
S
Department of Pediatrics, University of Rochester Medical Center, New York 14642.
Shapiro
D L
DL
Finkelstein
J N
JN
Notter
R H
RH
Johnston
C J
CJ
Quible
D J
DJ
D000818:Animals; D000831:Animals, Newborn; D001059:Apoproteins / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D010100:Oxygen / Q000633:toxicity*; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid; D019714:Tissue Inhibitor of Metalloproteinases
D001059:Apoproteins; D006023:Glycoproteins; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D019714:Tissue Inhibitor of Metalloproteinases; C046616:pulmonary surfactant apoprotein; D012313:RNA; D004247:DNA; D008666:Metalloendopeptidases; D010100:Oxygen