Epigenetics of idiopathic pulmonary fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. Recent work by our and other groups has identified strong genetic predisposition factors for the development of pulmonary fibrosis while cigarette smoke remains the most strongly associated environmental exposure risk factor. Gene expression profiling studies of IPF lung have taught us quite a bit about the biology of this fatal disease and those in peripheral blood have provided important biomarkers. However, epigenetic marks may be the missing link that connects the environmental exposure in genetically predisposed individuals to transcriptional changes associated with disease development. Moreover, epigenetic marks represent a promising therapeutic target for IPF. In this review, we will introduce the disease, summarize genetic and gene expression studies in IPF, discuss exposures relevant to IPF and known epigenetic changes associated with cigarette smoke exposure, and summarize epigenetic studies conducted so far in IPF. We will end by discussing limitations, challenges and future opportunities in this field.

Idiopathic pulmonary fibrosis and sleep disorders: no longer strangers in the night

“…Recent experimental evidence has emerged that DNA methylation is an important mechanism involved in IPF [110][111][112]. A comparative analysis of global DNA methylation examining 27 578 CpG islands combined with gene expression patterns from IPF and normal samples revealed that both DNA methylation and expression profiles were altered in IPF [113].…”

Relationship of DNA Methylation and Gene Expression in Idiopathic Pulmonary Fibrosis

“…In aggregate, these studies have consistently identified genes associated with ECM formation, degradation, signaling, smooth muscle markers, growth factors, developmental pathways, immunoglobulins, complement, and chemokines (4). The influence of cigarette smoking (5) and the dynamic gene expression changes (4) identified in IPF suggest that epigenetic mechanisms may influence the development of this disease (6). Early studies have demonstrated a link between exposure to tobacco smoke and lung cancer via methylation of CpG islands in cancer genes, such as p16 (7).…”

Personalised medicine in interstitial lung diseases

“…Downregulated miRNAs in IPF lungs include let-7d, miR-29 and the miR-200 family, while upregulated miRNAs include miR-155, miR-21, miR-199 and miR-154 [126,127].…”