University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands; Laboratory of Cancer Biology and Epigenetics, Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, P.R. China.
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands; Tianjin Medical University, School of Basic Medical Sciences, Department of Biochemistry and Molecular Biology, Department of Immunology, Tianjin, China.
Pharmacol Ther. 2018 Feb;182:1-14. doi: 10.1016/j.pharmthera.2017.08.007. Epub 2017 Aug 19.
Chronic obstructive pulmonary disease (COPD) is an age and smoking related progressive, pulmonary disorder presenting with poorly reversible airflow limitation as a result of chronic bronchitis and emphysema. The prevalence, disease burden for the individual, and mortality of COPD continues to increase, whereas no effective treatment strategies are available. For many years now, a combination of bronchodilators and anti-inflammatory corticosteroids has been most widely used for therapeutic management of patients with persistent COPD. However, this approach has had disappointing results as a large number of COPD patients are corticosteroid resistant. In patients with COPD, there is emerging evidence showing aberrant expression of epigenetic marks such as DNA methylation, histone modifications and microRNAs in blood, sputum and lung tissue. Therefore, novel therapeutic approaches may exist using epigenetic therapy. This review aims to describe and summarize current knowledge of aberrant expression of epigenetic marks in COPD. In addition, tools available for restoration of epigenetic marks are described, as well as delivery mechanisms of epigenetic editors to cells. Targeting epigenetic marks might be a very promising tool for treatment and lung regeneration in COPD in the future.
慢性阻塞性肺疾病（COPD）是一种与年龄和吸烟相关的进行性肺部疾病，表现为慢性支气管炎和肺气肿导致的气流受限不可逆转。COPD 的患病率、个体疾病负担和死亡率持续上升，而目前尚无有效的治疗策略。多年来，支气管扩张剂和抗炎皮质类固醇的联合治疗一直是治疗持续性 COPD 患者的最广泛应用方法。然而，由于大量 COPD 患者对皮质类固醇有抵抗力，这种方法的效果并不理想。在 COPD 患者中，有越来越多的证据表明，表观遗传标记（如 DNA 甲基化、组蛋白修饰和 microRNA）在血液、痰和肺组织中的表达异常。因此，使用表观遗传疗法可能存在新的治疗方法。本综述旨在描述和总结 COPD 中表观遗传标记异常表达的现有知识。此外，还描述了可用于恢复表观遗传标记的工具，以及表观遗传编辑物向细胞的传递机制。针对表观遗传标记可能是未来 COPD 治疗和肺再生的一个非常有前途的工具。
