Transcriptional and post-transcriptional control of liver gene expression during various physiologic and pathophysiologic states.
Transcriptional and post-transcriptional control of liver gene expression during various physiologic and pathophysiologic states.
复制标题
各种生理和病理生理状态下肝脏基因表达的转录和转录后控制。
DOI：
10.1055/s-2008-1040550
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发表时间：
1988
影响因子：
4.2
通讯作者：
Shafritz,DA
中科院分区：
文献类型：
--
作者：
Shafritz,DA
多种病理生理状态导致肝脏蛋白质合成异常。利用现代分子生物学技术，各研究小组现已开始从mRNA合成、代谢和功能等方面剖析调控肝脏基因表达的基本机制。在我们实验室，分子生物学的方法目前正在应用于影响肝功能的病理生理状态，如急性肝毒性、肝再生和肝纤维化的发展，肝脏特异性基因功能及其调控的异常已经被识别。本文的目的是综述最近几年的研究，这些研究表明转录和转录后事件在确定代表肝脏主要功能的特定mRNAs水平方面发挥着重要作用。我们的基本发现是，肝脏中特定基因表达的调节是一个动态的、活跃的和高度复杂的过程。转录后调控可以解释代表肝脏主要功能的基因表达的显著发育变化。在肝脏发育的不同阶段，主要的调控模式也从转录模式转变为转录后模式，一些多基因家族的成员也表现出独立的、有时是相反的调控模式。最后，在四氯化碳(CC1)诱导的大鼠肝硬变中，我们注意到肝脏再生反应的能力降低或去同步化，表明正常的细胞机制在这一过程中被破坏。人们希望分子生物学的工具将使我们能够进一步剖析这些异常并阐明其潜在的基础。
A variety of pathophysiologic states cause abnormalities in hepatic protein synthesis. By using techniques of modern molecular biology, various research groups are now beginning to dissect basic mechanisms regulating liver gene expression in terms of mRNA synthesis, metabolism, and function. In our laboratory, the methods of molecular biology are currently being applied to pathophysiologic states affecting liver function, such as acute hepatotoxicity, liver regeneration, and development of hepatic fibrosis, and abnormalities in liver-specific gene functions and their regulation have been identified. The purpose of this article is to review studies performed during the last few years which show that both transcriptional and post-transcriptional events play an important role in determining the level of specific mRNAs representing major functions of the liver. Our basic finding is that regulation of specific gene expression in the liver is a dynamic, active, and highly complex process. Post-transcriptional regulation accounts for significant developmental changes in expression of genes representing major functions of the liver. Examples have also been identified in which the primary mode of regulation changes from transcriptional to posttranscriptional at different stages of liver development, and some members of multigene families also show independent and sometimes contrasting modes of regulation. Finally, in carbon tetrachloride (CC1,)-induced cirrhosis in the rat, we have noted a reduced capacity or desynchronization of the liver regenerative response, indicating that normal cellular mechanisms have been disrupted during this process. It is hoped that the tools of molecular biology will permit us to dissect these abnormalities further and to elucidate their underlying basis.