The coordinated regulation of fibrinogen gene transcription by hepatocyte-stimulating factor and dexamethasone.
The coordinated regulation of fibrinogen gene transcription by hepatocyte-stimulating factor and dexamethasone.
复制标题
肝细胞刺激因子和地塞米松对纤维蛋白原基因转录的协调调节。
DOI：
10.1083/jcb.105.3.1067
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Fuller,GM
中科院分区：
文献类型：
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作者：
Otto,JM;Grenett,HE;Fuller,GM
糖皮质激素和肝细胞刺激因子（HSF;单核细胞/巨噬细胞衍生的多肽）是纤维蛋白原生物合成的有效调节剂。使用原代大鼠肝细胞和大鼠肝癌细胞系（FAZA），我们已经确定，更精确地说，这两个分子之间的相互作用，在控制纤维蛋白原的生产。当将地塞米松（DEX）或HSF加入细胞中时，纤维蛋白原的产生显著增加0.5-3倍。然而，如果两种药剂同时施用，则反应大得多，合成增加15-20倍。定量RNA分析表明，当这些因子单独存在时，只有HSF升高纤维蛋白原mRNA水平，但在DEX存在下，这种作用大大增强。这种模式也见于体外转录测定的结果中，所述体外转录测定允许定量分离的细胞核中的mRNA合成。放线菌酮不显着干扰增加转录所带来的HSF在任一细胞类型。然而，DEX增强被FAZA细胞中的放线菌酮阻断，从而表明在转化细胞中，蛋白质合成是发生最大转录所必需的。这里提供的数据表明，在纤维蛋白原基因表达的控制中需要两种类型的调节分子;增加转录的多肽激素（HSF）和增强多肽作用的类固醇（DEX）。
Glucocorticoids and hepatocyte-sth'nulating factor (HSF; a monocyte/macrophage-derived polypeptide) are potent regulators of fibrinogen biosynthesis. Using primary rat hepatocytes and a rat hepatoma cell line (FAZA) we have determined, more precisely, the interaction between these two molecules in the control of fibrinogen production. When dexamethasone (DEX) or HSF is added to the cells, there is a substantial increase in fibrinogen production 0.5-3-fold). However, if both agents are administered simultaneously the response is much greater with a 15-20-fold rise in synthesis. Quantitative RNA analysis demonstrates that when the factors are present individually only HSF elevates fibrinogen mRNA levels, but the effect is much enhanced in the presence of DEX. This pattern is also seen in the results of the in vitro transcription assays which allow quantitation of mRNA synthesis in isolated nuclei. Cycloheximide does not significantly interfere with the increased transcription brought about by HSF in either cell type. However, the DEX enhancement is blocked by cycloheximide in FAZA cells, thus indicating that in the transformed cell protein synthesis is required for maximal transcription to occur. Data presented here demonstrates the requirement for two types of regulator molecules in the control of fibrinogen gene expression; a polypeptide hormone (HSF) that increases transcription and a steroid (DEX) that enhances the action of the polypeptide.