Epigenetics in lung fibrosis: from pathobiology to treatment perspective

Abstract

Purpose of review: Idiopathic pulmonary fibrosis (IPF) is a fatal disease with limited treatment options and extensive gene expression changes identified in the lung parenchyma. Multiple lines of evidence suggest that epigenetic factors contribute to dysregulation of gene expression in IPF lung. Most importantly, risk factors that predispose to IPF - age, sex, cigarette smoke, and genetic variants - all influence epigenetic marks. This review summarizes recent findings of association of DNA methylation and histone modifications with the presence of disease and fibroproliferation.

Recent findings: In addition to targeted studies focused on specific gene loci, genome-wide profiles of DNA methylation demonstrate widespread DNA methylation changes in IPF lung tissue and a substantial effect of these methylation changes on gene expression. Genetic loci that have been recently associated with IPF also contain differentially methylated regions, suggesting that genetic and epigenetic factors act in concert to dysregulate gene expression in IPF lung.

Summary: Although we are in very early stages of understanding the role of epigenetics in IPF, the potential for the use of epigenetic marks as biomarkers and therapeutic targets is high and discoveries made in this field will likely bring us closer to better prognosticating and treating this fatal disease.

Figure 1

An overview of epigenetic regulation of gene expression in IPF lung. Environmental exposures such as cigarette smoke and genetic variants are associated with changes in epigenetic marks which in turn are associated with altered gene expression. Because the causative nature of these associations has not been established, these molecular processes are drawn as a circle with no arrows. * symbols on the chromosome view plot indicate approximate location of IPF-associated genetic loci from the two published GWAS (Fingerlin. Nat Genet. 2013;45:613–20 and Noth. Lancet Resp Med. 2013;1:309–17).