Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis

Fibrogenesis Tissue Repair. 2015 Oct 1;8:18. doi: 10.1186/s13069-015-0035-8. eCollection 2015.

Abstract

Fibrosis is a progressive and potentially fatal process that can occur in numerous organ systems. Characterised by the excessive deposition of extracellular matrix proteins such as collagens and fibronectin, fibrosis affects normal tissue architecture and impedes organ function. Although a considerable amount of research has focused on the mechanisms underlying disease pathogenesis, current therapeutic options do not directly target the pro-fibrotic process. As a result, there is a clear unmet clinical need to develop new agents. Novel findings implicate a role for epigenetic modifications contributing to the progression of fibrosis by alteration of gene expression profiles. This review will focus on DNA methylation; its association with fibroblast differentiation and activation and the consequent buildup of fibrotic scar tissue. The potential use of therapies that modulate this epigenetic pathway for the treatment of fibrosis in several organ systems is also discussed.

Keywords: 5-aza-2′-deoxycytidine; 5-azacytidine; DNA methylation; Fibroblast; Fibrosis; Myofibroblast.