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Epigenetic Regulation of Myofibroblast Phenotypes in Fibrosis

  • Activated Myofibroblasts and Fibrosis in Various Organs (T Kisseleva and Y Liu, Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

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.

Recent Findings

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.

Summary

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

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Funding

Thu Elizabeth Duong is a Fellow in the Pediatric Scientist Development Program. This project was supported by Award Number K12-HD000850 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The work in this publication was supported in part by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under Award Number U01HL122626 for J.S.H., as well as 1R01HL111169.

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  1. Division of Pediatric Respiratory Medicine, University of California–San Diego, Biomedical Research Facility 2, Room 2113, 9500 Gilman Dr. MC 0731, La Jolla, CA, 92093-0731, USA

    Thu Elizabeth Duong & James S. Hagood

  2. Division of Respiratory Medicine, Rady Children’s Hospital of San Diego, San Diego, CA, USA

    Thu Elizabeth Duong & James S. Hagood

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  1. Thu Elizabeth Duong
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Correspondence to James S. Hagood.

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Dr. Hagood reports personal fees from Kyowa Hakko Kirin, Co., Ltd., outside the submitted work.

Thu Elizabeth Duong declares no conflicts of interest.

Thu Duong and James Hagood declare that they have no conflict of interest.

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This article is part of the Topical Collection on Activated Myofibroblasts and Fibrosis in Various Organs

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Duong, T.E., Hagood, J.S. Epigenetic Regulation of Myofibroblast Phenotypes in Fibrosis. Curr Pathobiol Rep 6, 79–96 (2018). https://doi.org/10.1007/s40139-018-0155-0

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