Department of Gastroenterology, Ankara University Faculty of Medicine, Ankara, Turkey.
Department of Gastroenterology, Ege University Faculty of Medicine, İzmir, Turkey.
Turk J Gastroenterol. 2023 May;34(5):437-448. doi: 10.5152/tjg.2023.22515.
Inflammatory bowel diseases are multifactorial, chronic, continuous, relapsing, and immune-mediated diseases of the gastrointestinal tract. It has been believed that mechanisms underlying inflammatory bowel diseases include genetic predisposition, environmental factors, and altered immune response to the gut microbiome. The epigenetic modulation takes place via chromatin modifications, including phosphorylation, acetylation, methylation, sumoylation, and ubiquitination. The methylation levels of colonic tissue were found well correlated to blood samples in inflammatory bowel diseases. Moreover, the methylation level of specific genes was different between Crohn's disease and ulcerative colitis. It has been shown that the enzymes affecting histone modifications like histone deacetylases and histone acetyltransferases do not act solely on histones but also affect the acetylation of many proteins such as p53 and STAT3. It has been already shown that a nonselective histone deacetylase inhibitor, Vorinostat (SAHA), which is currently being used in several cancer treatments, showed anti-inflammatory activities in mouse models. Among epigenetic alterations, long non-coding RNAs and microRNAs play significant roles in T-cell maturation, differentiation, activation, and senility. The long non-coding RNA and microRNA expression profiles can perfectly separate inflammatory bowel disease patients from healthy controls and are remarked as biomarkers of inflammatory bowel diseases. Overall, many studies have shown that epigenetic inhibitors can target significant signal pathways in the pathogenesis of inflammatory bowel diseases, and the impact of epigenetic inhibitors is being studied in clinical trials. In conclusion, exploring more epigenetic pathways regarding inflammatory bowel disease pathogenesis will help us to discover therapeutic targets and new drugs and agents targeting miRNAs in inflammatory bowel diseases. In general, discovering epigenetic targets could improve the diagnosis and treatment of inflammatory bowel diseases.
炎症性肠病是一种多因素、慢性、持续、复发和免疫介导的胃肠道疾病。人们认为，炎症性肠病的发病机制包括遗传易感性、环境因素和对肠道微生物组的免疫反应改变。表观遗传调控通过染色质修饰发生，包括磷酸化、乙酰化、甲基化、SUMO 化和泛素化。在炎症性肠病中，发现结肠组织的甲基化水平与血液样本密切相关。此外，克罗恩病和溃疡性结肠炎之间特定基因的甲基化水平存在差异。已经表明，影响组蛋白修饰的酶，如组蛋白去乙酰化酶和组蛋白乙酰转移酶，不仅作用于组蛋白，还影响许多蛋白质如 p53 和 STAT3 的乙酰化。已经表明，一种非选择性组蛋白去乙酰化酶抑制剂，伏立诺他（SAHA），目前正在几种癌症治疗中使用，在小鼠模型中显示出抗炎活性。在表观遗传改变中，长非编码 RNA 和 microRNAs 在 T 细胞成熟、分化、激活和衰老中发挥重要作用。长非编码 RNA 和 microRNA 的表达谱可以完美地区分炎症性肠病患者和健康对照者，并被标记为炎症性肠病的生物标志物。总的来说，许多研究表明，表观遗传抑制剂可以靶向炎症性肠病发病机制中的重要信号通路，并且正在临床试验中研究表观遗传抑制剂的影响。总之，探索更多关于炎症性肠病发病机制的表观遗传途径将有助于我们发现治疗靶点和针对炎症性肠病的新药物和 miRNA 靶向药物。总的来说，发现表观遗传靶点可以改善炎症性肠病的诊断和治疗。
