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

Epigenetics and the Overhealing Wound: The Role of DNA Methylation in Fibrosis

Free PMC article

Epigenetics and the Overhealing Wound: The Role of DNA Methylation in Fibrosis

Roisin Neary et al. Fibrogenesis Tissue Repair. .
Free PMC article


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.


Fig. 1
Fig. 1
Epigenetic regulation of fibrotic gene expression profiles. The absence of DNA methylation permits gene transcription. DNA methylation, the addition of a methyl group to carbon 5 on the cytosine ring, is catalysed by the DNA methyltransferase enzymes. Methyl binding domain (MBD) proteins are recruited to methylated DNA and result in gene silencing by preventing transcription factor binding. Several genes associated with the development of fibrosis, highlighted in the figure, have been shown to undergo silencing as a result of DNA hypermethylation. It is likely that many other genes yet to be identified are also involved in the epigenetic regulation of fibrosis. These associations suggest the potential use of agents which target this methylating event for therapeutic use in fibrotic disease

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