Figure 1. Fibroblast to myofibroblast differentiation and the role of epigenetic modifications Following injury, fibroblasts differentiate into myofibroblasts. This process is encouraged by pro-fibrotic stimulants, such as transforming growth factor β (TGFβ), inflammatory cytokines and hypoxia. Under normal circumstances, wound-healing myofibroblasts contribute to tissue remodeling and repair and are eventually removed by apoptosis. In contrast, fibrotic myofibroblasts are hyperproliferative and continually secrete pro-fibrotic cytokines and collagens into their surrounding environment. These cells are resistant to apoptosis and are therefore continually present in the tissue. As this review highlights, DNA hypermethylation as well as histone modifications have been implicated in controlling this process. Hence, the use of DNA methyltransferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi) may be beneficial in preventing myofibroblast differentiation.