Altered expression of type I collagen, TGF-beta 1, and related genes in rat lung exposed to 85% O2.
The gene expressions of type I collagen and transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1 mRNA also significantly increased after 14, but not 4 or 6 days of 85% O2 exposure. TGF-beta 1 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-beta 1, 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-beta 1 synthesis.
Medical Research Council Group in Lung Development, Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada.
A M
AM
Moore
S
S
Buch
R N
RN
Han
B A
BA
Freeman
M
M
Post
A K
AK
Tanswell
D000818:Animals; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006023:Glycoproteins / Q000235:genetics; D008168:Lung / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D003094:Collagen; D010100:Oxygen