A Mechanistic Study of Cigarette Smoke-Induced COPD in C57BL/6 Mice: The changes in lung epigenome following smoking cessation or switching to aerosol from a prototypic modified risk


Authored by  N Sierro, M Talikka, J Hoeng, M Peitsch, AW Hayes, NV Ivanov

Presented at The Society of Toxicology Annual Meeting 2015     

Abstract

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is the major cause of chronic morbidity and mortality in the world1. It is defined as progressive, irreversible airflow limitation caused by the combined effects of emphysema, chronic bronchitis, and narrowing of the small airways2. In the western world cigarette smoke is the main etiological factor in the pathogenesis of COPD3. Even though aberrant histone modifications have been the focus of epigenetic studies around COPD4, some studies have indicated that DNA methylation might also play a role in the COPD pathology. p16 and GATA4 methylation has been associated with lower percent predicted FEV1 in sputum5. A larger scale analysis from white blood cells proposed DNA methylation as a possible biomarker of COPD. 70% of the identified 349 methylated CpG sites were outside of CpG islands and significantly associated with COPD severity6. In addition to the predictive value, such methylation patterns may identify new molecular pathways involved in COPD pathogenesis. Known mechanisms by which cigarette smoke modulates DNA methylation have been reviewed by Lee and Pausova.  

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