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
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
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DOI：
10.1172/jci112163
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
KANG, AH
中科院分区：
文献类型：
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作者：
RAGHOW, R;LURIE, S;KANG, AH
我们通过 Northern blot 分析，对叙利亚金仓鼠肺部编码前胶原 α1(I)、弹性蛋白、纤连蛋白和肌动蛋白的信使 RNA (mRNA) 进行了表征。虽然弹性蛋白、纤连蛋白和 β-肌动蛋白各自由大小分别为 4.1 kb、9.1 kb 和 2.1 kb 的单一 mRNA 种类编码，但我们在仓鼠肺中鉴定出主要 (5.4 kb) 和次要 (6.5 kb) 前胶原 α1(I) mRNA 种类。三种mRNA的mRNA相对增加和最大积累的时间。治疗后 2-3 周达到峰值水平后，前胶原 α1(I) 和弹性蛋白 mRNA 的水平在第四周左右下降至接近正常值。相反，纤连蛋白mRNA的积累在博莱霉素治疗后第一周达到最大。与编码纤连蛋白的mRNA增加五倍相比，前胶原α1(I) mRNA的积累最为显着（比未治疗动物的水平高出七倍）。弹性蛋白 mRNA 比对照值增加大约两倍。核径流转录实验表明，编码原胶原α1(I)、纤连蛋白和弹性蛋白的基因的转录率选择性增加；前胶原α1(I)和纤连蛋白基因的转录刺激程度显着大于弹性蛋白。由于肌动蛋白 mRNA 的量以及肌动蛋白基因的转录率在博莱霉素处理后仅略有变化，因此我们得出结论，编码细胞外基质蛋白的 mRNA 的代谢可能在肺纤维化过程中优先受到干扰。
We have characterized the messenger RNAs (mRNAs) coding or 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 as 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 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.