Altered expression of type I collagen, TGF-β₁, and related genes in rat lung exposed to 85% O₂

The gene expressions of type I collagen and transforming growth factor- β₁ (TGF-β₁) were studied in lung tissue of rats exposed to air or 85% O₂ for 14 days. Peak expression of type I collagen mRNA was observed by 14 days of 85% O₂ exposure, at the same time as maximal immunoreactive type I collagen, which was most marked surrounding the major airways and vessels. TGF-β₁ mRNA also significantly increased after 14, but not 4 or 6, days of 85% O₂ exposure. TGF-β₁ immunoreactivity was only detected on day 14 of 85% O₂ exposure and was localized primarily to the pulmonary epithelium. As an increase in immunoreactive type I collagen was evident by day 6 of O₂ exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expressions of interstitial collagenase and TIMP preceded those of type I collagen and TGF-β₁, occurring at 4-6 days of exposure to 85% O₂, while there was no significant change in stromelysin mRNA. These findings are compatible with the initial O₂-mediated 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-β₁ synthesis.