Analysis of gene expression profile induced by hepatocyte nuclear factor 4α in hepatoma cells using an oligonucleotide microarray
Analysis of gene expression profile induced by hepatocyte nuclear factor 4α in hepatoma cells using an oligonucleotide microarray
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DOI：
10.1074/jbc.m105403200
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发表时间：
2002-04-19
影响因子：
4.8
通讯作者：
Moriwaki, H
中科院分区：
文献类型：
--
作者：
Naiki, T;Nagaki, M;Moriwaki, H
肝细胞核因子4α（HNF - 4α）是一种肝脏特异性转录因子，在许多肝脏特异性功能中发挥重要作用，包括脂质、葡萄糖、药物和氨代谢，以及胚胎肝脏发育。然而，其功能和调控机制尚未完全明确。在本研究中，我们构建了一种携带大鼠HNF - 4α cDNA的腺病毒载体，并将该腺病毒转染人肝癌细胞HuH - 7，以强制表达外源性HNF - 4α基因。我们利用包含9000多个基因的cDNA微阵列技术分析了HNF - 4α诱导的基因。结果显示，病毒转染后有62个基因的表达水平变化超过2.0倍。其中56个基因在HNF - 4α过表达时持续被诱导，6个基因被抑制。为了评估HNF - 4α的功能，我们尝试对这些基因进行分类，这些基因在先前的报告中已按照其编码蛋白的功能进行了分类。我们能够对45个基因进行分类。其余的HNF - 4α敏感基因未分类（4个基因）或未被鉴定（13个基因）。在已分类的基因中，几乎一半的诱导基因（40个中的26个）与代谢基因相关，特别是与脂质代谢相关基因有关。这种cDNA微阵列分析表明，HNF - 4α是肝脏代谢的核心调节因子之一。
Hepatocyte nuclear factor 4alpha (HNF-4alpha), a liver-specific transcription factor, plays a significant role in many liver-specific functions, including lipid, glucose, drug, and ammonia metabolism, and also in embryonal liver development. However, its functions and regulation are not yet clearly understood. In this study, we constructed an adenovirus vector carrying rat HNF-4alpha cDNA and transfected the adenovirus to human hepatoma cells, HuH-7, to enforce expression of the exogenous HNF-4alpha gene. We analyzed HNF-4alpha-induced genes using cDNA microarray technology, which included over 9000 genes. As a result, 62 genes showed a greater than 2.0-fold change in expression level after the viral transfection. Fifty-six genes were consistently induced by HNF-4alpha overexpression, and six genes were repressed. To assess HNF-4alpha function, we attempted to classify the genes, which had been classified by their encoding protein functions in a previous report. We could classify 45 genes. The rest of the HNF-4alpha-sensitive genes were unclassified (4 genes) or not identified (13 genes). Among the classified genes, almost half of the induced genes (26 of 40) were related to metabolism genes and particularly to lipid metabolism-related genes. This cDNA microarray analysis showed that HNF-4alpha is one of the central liver metabolism regulators.