Epigenetic Regulation of Myofibroblast Phenotypes in Fibrosis

Myofibroblasts are the fundamental drivers of fibrosing disorders; there is great value in better defining epigenetic networks involved in myofibroblast behavior. Complex epigenetic paradigms, which are likely organ and/or disease specific, direct pathologic myofibroblast phenotypes. In this review, we highlight epigenetic regulators and the mechanisms through which they shape myofibroblast phenotype in fibrotic diseases of different organs.

Hundreds of genes and their expression contribute to the myofibroblast transcriptional regime influencing myofibroblast phenotype. An increasingly large number of epigenetic modifications have been identified in the regulation of these signaling pathways driving myofibroblast activation and disease progression. Drugs that inhibit or reverse profibrotic epigenetic modifications have shown promise in vitro and in vivo; however, no current epigenetic therapies have been approved to treat fibrosis. Newly described epigenetic mechanisms will be mentioned, along with potential therapeutic targets and innovative strategies to further understand myofibroblast-directed fibrosis.

Epigenetic regulators that direct myofibroblast behavior and differentiation into pathologic myofibroblast phenotypes in fibrotic disorders comprise both overlapping and organ-specific epigenetic mechanisms.