Ajoolabady Amir, Aslkhodapasandhokmabad Hamid, Zhou Yuan, Ren Jun
School of Pharmacy, University of Wyoming College of Health Sciences, Laramie, Wyoming, USA.
Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital Fudan University, Shanghai, China.
Med Res Rev. 2022 Jul;42(4):1463-1491. doi: 10.1002/med.21881. Epub 2022 Feb 21.
Alcohol-related liver disease (ARLD) refers to a spectrum of hepatic damage triggered by excessive alcohol intake, resulting in inflamed and swollen livers, ultimately, liver cirrhosis. Alcoholic liver disease (ALD) is a similar term denoting liver disorders encompassing steatosis, cirrhosis, and hepatocellular carcinoma. Recent evidence has suggested a vital role for epigenetic factors, which modulate gene expression in the absence of changes in DNA sequence, in the onset and progression of liver disorders, to foster hepatic fibrogenesis and cirrhosis. Mounting findings have delineated that alcohol consumption extensively modulates liver epigenetics, thus, prompting the etiology of ARLD and ALD. Alcohol-induced epigenetic modifications (AIEM) in the liver encompass histone modification, microRNA-induced genetic modulation, DNA methylation, and alcohol-evoked cell signaling that alters gene expression. Herein, we aim at summarizing key findings to decipher AIEM and its role in the onset and development of ARLD and ALD from the perspectives of both cellular and animal models of alcohol exposure. Furthermore, we will share our viewpoints on epigenetics-based therapeutic options in the management of ARLD and ALD.
酒精性肝病（ARLD）是指因过量饮酒引发的一系列肝脏损伤，导致肝脏发炎和肿大，最终发展为肝硬化。酒精性肝病（ALD）是一个类似的术语，指包括脂肪变性、肝硬化和肝细胞癌在内的肝脏疾病。最近的证据表明，表观遗传因素在肝脏疾病的发生和发展中起着至关重要的作用，这些因素在DNA序列不变的情况下调节基因表达，促进肝纤维化和肝硬化。越来越多的研究结果表明，饮酒会广泛调节肝脏表观遗传学，从而引发ARLD和ALD的病因。肝脏中酒精诱导的表观遗传修饰（AIEM）包括组蛋白修饰、微小RNA诱导的基因调节、DNA甲基化以及酒精引发的改变基因表达的细胞信号传导。在此，我们旨在从酒精暴露的细胞和动物模型两个角度总结关键发现，以解读AIEM及其在ARLD和ALD发生发展中的作用。此外，我们将分享我们对基于表观遗传学的治疗方案在ARLD和ALD管理中的观点。
