Increased DNA methylation in the livers of patients with alcoholic hepatitis.
Increased DNA methylation in the livers of patients with alcoholic hepatitis.
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DOI：
10.1016/j.yexmp.2015.08.001
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发表时间：
2015-10
影响因子：
3.6
通讯作者：
French SW
中科院分区：
文献类型：
--
作者：
Shen H;French BA;Tillman BC;Li J;French SW
基因表达的表观遗传调控在酒精性肝炎（AH）的发展中发挥着关键作用。尽管已经表明，由蛋氨酸代谢变化引起的乙醇诱导的肝细胞损伤会导致肝细胞中整体基因表达的变化，但表观遗传机制在这一过程中的作用几乎没有被研究过。 5-甲基胞嘧啶 (5mC) 和 5-羟甲基胞嘧啶 (5hmC) 是表观遗传 DNA 修饰的主要分子，在基因表达的控制中发挥重要作用。使用针对 5mC 和 5hmC 的抗体，通过免疫组织化学检查 AH 患者的 DNA 甲基化，并通过形态测量图像分析进行定量。 AH 患者的 5mC 免疫反应强度显着高于正常对照。虽然AH患者5-hmC有下降趋势，但AH患者与正常对照之间差异不显着。我们的研究表明异常 DNA 甲基化与 AH 的发病机制相关。
Epigenetic regulation of gene expression has been suggested to play a critical role in the development of alcoholic hepatitis (AH). Although it has been shown that ethanol-induced damage in hepatocytes resulted from a change in methionine metabolism causes global gene expression changes in hepatocytes, the role of the epigenetic machinery in such processes has, however, been barely investigated. 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are major molecules of epigenetic DNA modification that play an important role in the control of gene expression. Using antibodies against 5mC and 5hmC, the DNA methylation in patients with AH was examined by immunohistochemistry and quantified by morphometric image analysis. The immunoreactivity intensity of 5mC in patients with AH was significantly higher than that seen in normal controls. While there was a trend of decreased 5-hmC in patients with AH, the difference between patients with AH and normal control was not significant. Our study suggests that aberrant DNA-methylation is associated pathogenesis of AH.