Epigenetics in fibrosis

Fibrosis is a common and important disease. It is a pathological state due to excessive scar formation mediated by an increase in activated fibroblasts that express alpha smooth muscle actin and copious amounts of extracellular matrix molecules. Epigenetics is an area of research that encompasses three main mechanisms: methylation, histone modifications to the tails of histones and also non-coding RNAs including long and short non-coding RNAs. These three mechanisms all seek to regulate gene expression without a change in the underlying DNA sequence. In recent years an explosion of research, aided by deep sequencing technology becoming available, has demonstrated a role for epigenetics in fibrosis, either organ specific like lung fibrosis or more widespread as in systemic sclerosis. While the great majority of epigenetic work in fibrosis is centered on histone codes, more recently the non-coding RNAs have been examined in greater detail. It is known that one modification can affect the other and cross-talk among all three adds a new layer of complexity. This review aims to examine the role of epigenetics in fibrosis, evaluating all three mechanisms, and to suggest possible areas where epigenetics could be targeted therapeutically.