The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model
The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model
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DOI：
10.1016/j.jhep.2008.10.020
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发表时间：
2009-03-01
影响因子：
25.7
通讯作者：
Ingelman-Sundberg, Magnus
中科院分区：
文献类型：
--
作者：
Butura, Angelica;Nilsson, Kerstin;Ingelman-Sundberg, Magnus
背景/目的：CYP2E1代谢乙醇，产生活性氧，被认为在酒精性肝病的发展中起重要作用。本研究旨在利用转基因人CYP2E1基因的小鼠，评估CYP2E1与乙醇联合在酒精性肝病发展中的作用。方法：采用Affymetrix微阵列技术和TaqMan RealTime PCR技术，对转染人CYP2E1基因的小鼠和对照组进行肝脏基因表达变化监测，分别用乙醇或等热量葡萄糖灌胃处理4周。结果：CYP2E1基因的存在加重了肝损伤，增加了应激相关基因的表达。微阵列分析显示，结构基因的表达，特别是细胞角蛋白8和18，与病理高度相关。结论：这项体内研究证实了先前仅在体外发现的关于CYP2E1和酒精的一些发现。这些结果提供了CYP2E1过表达加重肝损伤的体内证据，并提示细胞角蛋白8和18的表达可被认为是酒精性肝病进展的生物标志物。(C) 2009年欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: CYP2E1 metabolizes ethanol, generates reactive oxygen species, and is suggested to be important for development of alcoholic liver disease. The present study aims to evaluate the role of CYP2E1 in combination with ethanol for development of alcoholic liver disease using mice transgenic for the human CYP2E1 gene.Methods: Changes in hepatic gene expression were monitored in controls and mice transgenic for human CYP2E1, treated with ethanol or isocaloric dextrose intragastrically for 4 weeks, and related to pathology using Affymetrix microarrays and TaqMan RealTime PCR.Results: Presence of the CYP2E1 transgene increased liver injury and increased expression of stress related genes. Microarray analyses revealed the expression of structural genes, particularly cytokeratin 8 and 18, to be highly related to pathology.Conclusions: This in vivo study confirms several findings regarding CYP2E1 and alcohol previously found only in vitro. These results provide in vivo evidence that CYP2E1 overexpression aggravates hepatic injury, and suggest that expression of cytokeratins 8 and 18 can be considered as biomakers for the progression of alcoholic liver disease. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.