GENE-EXPRESSION OF TYPE-I, TYPE-III AND TYPE-IV COLLAGENS IN HEPATIC-FIBROSIS INDUCED BY DIMETHYLNITROSAMINE IN THE RAT
GENE-EXPRESSION OF TYPE-I, TYPE-III AND TYPE-IV COLLAGENS IN HEPATIC-FIBROSIS INDUCED BY DIMETHYLNITROSAMINE IN THE RAT
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DOI：
10.1042/bj2440075
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发表时间：
1987-05-15
影响因子：
4.1
通讯作者：
SAVOLAINEN, ER
中科院分区：
文献类型：
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作者：
ALAKOKKO, L;PIHLAJANIEMI, T;SAVOLAINEN, ER
以二甲基亚硝胺（DMN）诱导的肝纤维化为实验模型，研究肝纤维化过程中胶原基因的表达。I型、III型和IV型胶原mRNA浓度的增加被发现是肝纤维化发展的早期事件，因为在DMN治疗的第7天，所有三种胶原的mRNA都显示出明确的增加趋势。脯氨酸4-羟化酶（EC 1.14.11.2）和半乳糖羟基赖氨酸葡萄糖基转移酶（EC 2.4.1.66）活性在此阶段也明显升高，而肝脏胶原含量未见增加。在所有研究的时间点上，I型胶原蛋白mrna的增加最小，而IV型胶原蛋白mrna的增加最大。DMN处理第21天，三种胶原蛋白mrna的相对浓度分别为ⅰ型胶原蛋白的350%、ⅲ型胶原蛋白的490%和ⅳ型胶原蛋白的660%。数据进一步表明，正常大鼠肝脏中三种胶原蛋白mrna的比例分别为1.0:0.9:0.2，DMN处理第14天为1.0:1.4:0.8,21天为1.0:1.3:0.5。IV型胶原mRNA的早期显著增加表明，基底膜胶原蛋白的增强可能是肝纤维化发展的早期事件。
Dimethylnitrosamine (DMN)-induced hepatic fibrosis was used as an experimental model to study collagen-gene expression during liver fibrogenesis. Increase in the concentrations of the mRNA for type I, III and IV collagens was found to be an early event in the development of hepatic fibrosis, as the mRNAs for all three collagen types showed a definite increasing tendency by day 7 of DMN treatment. Prolyl 4-hydroxylase (EC 1.14.11.2) and galactosylhydroxylysyl glucosyltransferase (EC 2.4.1.66) activities were also distinctly elevated at this stage, whereas no increase could be detected in the liver collagen content. The increase in the mRNAs for type I collagen was the smallest and that for type IV collagen the greatest at all the time points studied. The relative concentrations of the mRNAs for the three collagen types on day 21 of DMN treatment were 350% of the control mean for type I collagen, 490% for type III and 660% for type IV. The data further indicate that the proportions of the mRNAs for the three collagen types are 1.0:0.9:0.2 in normal rat liver, 1.0:1.4:0.8 on day 14 of DMN treatment, and 1.0:1.3:0.5 on day 21. The early marked increase in the mRNA for type IV collagen suggests that enhanced production of basement-membrane collagen may be an early event in the development of hepatic fibrosis.