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 tobacco product

      Sierro, N.; Talikka, M.; Hoeng, J.; Peitsch, M. C.; Hayes, A. W.; Ivanov, N. V.

      Conference date
      Mar 23, 2015
      Conference name
      Society of Toxicology (SOT) 2015

      Introduction: Chronic Obstructive Pulmonary Disease (COPD) is the major cause of chronic morbidity and mortality in the world. It is defined as progressive, irreversible airflow limitation caused by the combined effects of emphysema, chronic bronchitis, and narrowing of the small airways. In the western world cigarette smoke is the main etiological factor in the pathogenesis of COPD. Even though aberrant histone modifications have been the focus of epigenetic studies around COPD, 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 sputum. 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 severity. 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.