Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery.
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide. The growing burden of COPD is due to continuous tobacco use, which is the most important risk factor of the disease, indoor fumes, occupational exposures and also aging of the world's population. Epigenetic mechanisms significantly contribute to COPD pathophysiology.


METHODS
This review focuses on disease-relevant changes in DNA modification, histone modification and non-coding RNA expression in COPD, and provides insight into novel therapeutic approaches modulating epigenetic mechanisms. Recent findings revealed, among others, globally changed DNA methylation patterns, decreased levels of histone deacetylases and reduced microRNAs levels in COPD. The authors also discuss a potential role of the chromatin silencing Polycomb group of proteins in COPD.


CONCLUSIONS
COPD is a highly complex disease and therapy development is complicated by the fact that many smokers develop both COPD and lung cancer. Of interest, combination therapies involving DNA methyltransferase inhibitors and anti-inflammatory drugs provide a promising approach, as they might be therapeutic for both COPD and cancer. Although the field of epigenetic research has virtually exploded over the last 10 years, particular efforts are required to enhance our knowledge of the COPD epigenome in order to successfully establish epigenetic-based therapies for this widespread disease.
Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München, University Hospital and Ludwig-Maximilians-University, Member of the German Center for Lung Research (DZL) , Max-Lebsche-Platz 31, 81377 Munich , Germany.
Andrea C
AC
Schamberger
Nikica
N
Mise
Silke
S
Meiners
Oliver
O
Eickelberg
D000818:Animals; D004247:DNA / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism; D006801:Humans; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D022661:RNA, Untranslated / Q000378:metabolism; D012307:Risk Factors
D006657:Histones; D022661:RNA, Untranslated; D004247:DNA
Biomarker; DNA methyltransferase inhibitors; DNA modification; Polycomb; chronic obstructive pulmonary disease; emphysema; histone deacetylase activators