More than a Genetic Code: Epigenetics of Lung Fibrosis

Abstract

At the end of the last century, genetic studies reported that genetic information is not transmitted solely by DNA, but is also transmitted by other mechanisms, named as epigenetics. The well-described epigenetic mechanisms include DNA methylation, biochemical modifications of histones, and microRNAs. The role of altered epigenetics in the biology of various fibrotic diseases is well-established, and recent advances demonstrate its importance in the pathogenesis of pulmonary fibrosis-predominantly referring to idiopathic pulmonary fibrosis, the most lethal of the interstitial lung diseases. The deficiency in effective medications suggests an urgent need to better understand the underlying pathobiology. This review summarizes the current knowledge concerning epigenetic changes in pulmonary fibrosis and associations of these changes with several cellular pathways of known significance in its pathogenesis. It also designates the most promising substances for further research that may bring us closer to new therapeutic options.

Fig. 1

The sequence of events including impaired DNA methylation that leads to pulmonary fibrosis. α-SMA α-smooth muscle actin, BMP bone morphogenetic protein, BMPER BMP endothelial cell precursor-derived regulator, CARD10 caspase recruitment domain-containing protein 10, Cav-1 caveolin 1, CDKN2B a cyclin-dependent kinase 4 inhibitor B, EBF3 early B-cell factor 3, EP2 prostaglandin E₂ receptor subtype EP2, MeCP2 methyl CpG binding protein, MGMT O⁶-alkylguanine DNA alkyltransferase, PARP1 poly(ADP-ribose)polymerase 1, SFRP secreted fizzled protein, TGF-β transforming growth factor β, Thy-1 thymocyte differentiation antigen 1, TLR9 toll-like receptor 9