Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state
Position-specific gene expression in the liver lobule is directed by the microenvironment and not by the previous cell differentiation state
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DOI：
10.1074/jbc.274.4.2157
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发表时间：
1999-01-22
影响因子：
4.8
通讯作者：
Gorla, GR
中科院分区：
文献类型：
--
作者：
Gupta, S;Rajvanshi, P;Gorla, GR
指导位置特异性肝脏基因调控的机制还不完全清楚。为了确定这方面的肝脏基因表达是否是一个根深蒂固的现象，我们使用移植的肝细胞作为报告在二肽基肽酶IV缺陷的F344大鼠。在肝实质中整合后，移植细胞的位置通过四氯化碳靶向肝消融从门静脉周围区域转移到静脉周围区域。在对照组中，移植细胞在门静脉周围区域显示出更高的葡萄糖-6-磷酸酶和更少的糖原含量。当移植细胞从门静脉周围转移到静脉周围时，这种模式被逆转。肝细胞移植后，门静脉周围肝细胞的细胞色素P450活性明显降低，而门静脉周围肝细胞的细胞色素P450活性明显降低。然而，门静脉周围细胞在培养条件下迅速获得这种设施。这些发现表明，肝脏微环境在指导位置特异性基因表达方面优于细胞的先前分化状态。因此，特化肝细胞功能的持续性将需要与调控信号和底物可用性的相互作用，这取决于对肝脏基因调控的进一步分析，包括在祖细胞和/或干细胞中。
Mechanisms directing position-specific liver gene regulation are incompletely understood. To establish whether this aspect of hepatic gene expression is an inveterate phenomenon, we used transplanted hepatocytes as reporters in dipeptidyl peptidase IV-deficient F344 rats. After integration in liver parenchyma, the position of transplanted cells was shifted from periportal to perivenous areas by targeted hepatic ablations with carbon tetrachloride, In controls, transplanted cells showed greater glucose-6-phosphatase and lesser glycogen content in periportal areas. This pattern was reversed when transplanted cells shifted from periportal to perivenous areas. Transplanted hepatocytes in perivenous areas exhibited inducible cytochrome P450 activity, which was deficient in periportal hepatocytes, Moreover, cytochrome P450 activity was rapidly extinguished in activated hepatocytes when these cells were transplanted into the nonpermissive river of suckling rat pups, In cells isolated from the normal F344 rat liver, cytochrome P450 inducibility was originally greater in perivenous hepatocytes; however, periportal cells rapidly acquired this facility in culture conditions. These findings indicate that the liver microenvironment exerts supremacy over prior differentiation state of cells in directing position-specific gene expression. Therefore, persistence of specialized hepatocellular function will require interactions with regulatory signals and substrate availability, which bears upon further analysis of liver gene regulation, including in progenitor and/or stem cells.