Shukla Shivendra D, Lim Robert W
Department of Medical Pharmacology & Physiology, School of Medicine, University of Missouri, Columbia, Missouri, USA.
Alcohol Res. 2013;35(1):47-55.
The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)-hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.
表观遗传调控机制的网络不断扩展，也涵盖了乙醇诱导的胃肠（GI）-肝脏系统变化。在过去几年中，越来越多的证据确凿地表明，酒精会改变胃肠道和肝脏中的多个表观遗传参数。受影响的主要途径包括DNA甲基化、组蛋白的不同位点特异性修饰以及微小RNA。乙醇代谢、细胞信号级联反应和氧化应激与这些反应有关。此外，乙醇诱导的脂肪肝（即脂肪性肝炎）和肝癌（即肝细胞癌）的进展可能是表观遗传学改变的结果。通过表观遗传变化对基因和/或蛋白质表达的修饰也可能有助于胃肠道和肝脏之间的相互作用以及涉及其他器官的全身变化。因此，乙醇的表观遗传效应可能在乙醇通过肝脏-GI轴介导的多个器官诱导的各种病理生理反应中起核心作用。
