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Pharmacol Ther. 2018 Feb;182:1-14. doi: 10.1016/j.pharmthera.2017.08.007. Epub 2017 Aug 19.

The potential for targeted rewriting of epigenetic marks in COPD as a new therapeutic approach.

Author information

1
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.
2
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.
3
Early Life Origins of Chronic Lung Disease, Priority Area Asthma & Allergy, Leibnitz Center for Medicine and Biosciences, Research Center Borstel and Christian Albrechts University Kiel; Airway Research Center North, member of the German Center for Lung Research (DZL), Germany.
4
University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, The Netherlands.
5
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. Electronic address: m.n.hylkema@umcg.nl.

Abstract

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.

KEYWORDS:

COPD; DNA methylation; Delivery; Epigenetic editing; Histone modification; microRNA

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