ALTERED EXPRESSION OF TYPE-I COLLAGEN, TGF-BETA(1), AND RELATED GENESIN RAT LUNG EXPOSED TO 85-PERCENT O-2

The gene expressions of type I collagen and transforming growth factor -pi (TGF-beta(1)) were studied in lung tissue of rats exposed to air o r 85% O-2 for 14 days. Peak expression of type I collagen mRNA was obs erved by 14 days of 85% O-2 exposure, at the same time as maximal immu noreactive type I collagen, which was most marked surrounding the majo r airways and vessels. TGF-beta(1) mRNA also significantly increased a fter 14, but not 4 or 6, days of 85% O-2 exposure. TGF-beta(1) immunor eactivity was only detected on day 14 of 85% O-2 exposure and was loca lized primarily to the pulmonary epithelium. As an increase in immunor eactive type I collagen was evident by day 6 of O-2 exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expres sions of interstitial collagenase and TIMP prec eded those of type I collagen and TGF-beta(1), occurring at 4-6 days o f exposure to 85% O-2, while there was no significant change in strome lysin mRNA. These findings are compatible with the initial O-2-mediate d increase in type I collagen deposition being a result of an altered proteinase/antiproteinase balance in the lung, and the subsequent more marked deposition being a response to increased TGF-beta(1) synthesis .