Profiles of steady state levels of messenger RNAs coding for type I procollagen, elastin, and fibronectin in hamster lungs undergoing bleomycin-induced interstitial pulmonary fibrosis.
We have characterized the messenger RNAs (mRNAs) coding for procollagen alpha 1(I), elastin, fibronectin, and actin in the lungs of Syrian golden hamsters by Northern blot analyses. While elastin, fibronectin, and beta-actin were each coded for by a single mRNA species of 4.1 kilobases (kb), 9.1 kb, and 2.1 kb in size, respectively, we identified a major (5.4 kb) and a minor (6.5 kb) procollagen alpha 1(I) mRNA species in the hamster lungs. The mRNAs for the three extracellular matrix proteins showed increased accumulation followed by steady decline in the bleomycin-treated lungs. There were significant differences among the three mRNAs in the relative increase and the time of maximum accumulation. After reaching the peak levels between 2-3 wk posttreatment, the levels of procollagen alpha 1(I) and elastin mRNAs declined to near normal values around the fourth week. In contrast, the accumulation of fibronectin mRNA was maximum in the first week after bleomycin treatment. The procollagen alpha 1(I) mRNA accumulated most dramatically (sevenfold above the levels in the untreated animals) compared with a five-fold increase in mRNA coding for fibronectin. Elastin mRNA increased approximately twofold above the control values. Nuclear runoff transcription experiments demonstrated a selective increase in the rates of transcription of genes coding for procollagen alpha 1(I), fibronectin, and elastin; the extent of transcriptional stimulation of procollagen alpha 1(I) and fibronectin genes was significantly greater than that of elastin. Since the amount of actin mRNA, as well as the rate of transcription of actin gene(s), varied only slightly after bleomycin treatment, we conclude that the metabolism of mRNAs coding for extracellular matrix proteins may be preferentially perturbed during pulmonary fibrosis.
Raghow
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R
Lurie
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Seyer
J M
JM
Kang
A H
AH
D000199:Actins / Q000235:genetics; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D006224:Cricetinae; D004549:Elastin / Q000235:genetics*; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D008168:Lung / Q000378:metabolism; D011347:Procollagen / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D000199:Actins; D005353:Fibronectins; D011347:Procollagen; D012333:RNA, Messenger; D001761:Bleomycin; D004549:Elastin