Epigenetic regulation of pulmonary inflammation

Abstract

Pulmonary disease such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and pulmonary hypertension are the leading cause of deaths. More importantly, lung diseases are on the rise and environmental factors induced epigenetic modifications are major players on this increased prevalence. It has been reported that dysregulation of genes involved in epigenetic regulation such as the histone deacetylase (HDACs) and histone acetyltransferase (HATs) play important role in lung health and pulmonary disease pathogenesis. Inflammation is an essential component of respiratory diseases. Injury and inflammation trigger release of extracellular vesicles that can act as epigenetic modifiers through transfer of epigenetic regulators such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), proteins and lipids, from one cell to another. The immune dysregulations caused by the cargo contents are important contributors of respiratory disease pathogenesis. N6 methylation of RNA is also emerging to be a critical mechanism of epigenetic alteration and upregulation of immune responses to environmental stressors. Epigenetic changes such as DNA methylation are stable and often long term and cause onset of chronic lung conditions. These epigenetic pathways are also being utilized for therapeutic intervention in several lung conditions.

Keywords: Epigenetics; Exosomes; Lung; Pulmonary disease; Therapies.

Figure 1.

Schematic representation of epigenetic regulation in pulmonary inflammation and disease. PAD: peptidyl arginine deiminase; R: arginine; Cit: citrulline; Me: methyl; HMT: histone methyl transferase; HDMT histone demethyltransferases; Ac: acetyl; lncRNA: lncRNA: long non coding RNA; m6A: N6-Methyladenosine; miRNA: microRNA; MVB, microvesicular bodies.