Gene expression patterns of the liver in response to alcohol: In vivo and in vitro models compared

Gene expression patterns of the liver in response to alcohol: In vivo and in vitro models compared
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DOI:
10.1016/j.yexmp.2005.12.006
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发表时间:
2006-06-01
影响因子:
3.6
通讯作者:
French, Samuel W.
French, Samuel W.
中科院分区:
医学3区
文献类型:
--
作者:
Bardag-Gorce, Fawzia;French, Barbara A.;French, Samuel W.

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酒精性肝病发病机制存在两种基本模型,一种在体内,一种在体外。为了证明体外模型的合理性,需要证据表明其模拟体内模型。因此,使用两种模型比较了高乙醇水平引起的基因表达变化。在两种模型中,许多功能途径都上调。这些信号通路包括胰岛素信号通路、TGF β信号通路、细胞凋亡、MAPK信号通路、writ信号通路和细胞凋亡。在体内上调的脂肪酸合成途径和体内下调的糖基化酶中发现了差异。此外,在体外下调的是线粒体和翻译因子的β氧化。线粒体过氧化氢酶和超氧化物歧化酶在体外上调。这两种酶具有抗氧化作用。总之,在测试的体内和体外模型中发现了对高酒精水平的基因表达途径变化形式的显著相似的反应。(c)2006年爱思唯尔公司All rights reserved.
Two basic models of alcoholic liver disease pathogenesis exist, one in vivo and one in vitro. To justify the in vitro model, evidence is needed to show that it simulates the in vivo model. Therefore, changes in gene expression caused by high ethanol levels were compared using the two models. Many functional pathways were upregulated in both models. These included the insulin signaling pathway, TGF beta signaling pathway, apoptosis, MAPK signaling pathway, writ signaling pathway and apoptosis. Differences were found in the fatty acids synthesis pathway, which was upregulated in vivo; and glycosylation enzymes which were downregulated in vivo. Also, downregulated in vitro were beta oxidation by mitochondria and translation factors. Catalase and superoxide dismutase in mitochondria were upregulated in vitro. These two enzymes have antioxidant effects. In summary, remarkably similar responses to high alcohol levels in the form of changes in gene expression pathways were found in the in vivo and in vitro models tested. (c) 2006 Elsevier Inc. All rights reserved.