Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Volume 1863, Issue 9, Pages 2389-2397Publisher
ELSEVIER
DOI: 10.1016/j.bbadis.2017.05.010
Keywords
DNA methylation; DNA methylation inhibitors; Gene expression; Organ fibrosis; Epigenetics; Myofibroblasts
Funding
- National Natural Science Foundation of China [81470256]
- US grant [VA BX003056]
- NIH grants [P01HL14470, R01AG050567]
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DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA interference, results in heritable changes in gene expression independent of alterations in DNA sequence. Epigenetic regulation often occurs in response to aging and environment stimuli, including exposures and diet. Studies have shown that DNA methylation is critical in the pathogenesis of fibrosis involving multiple organ systems, contributing to significant morbidity and mortality. Aberrant DNA methylation can silence or activate gene expression patterns that drive the fibrosis process. Fibrosis is a pathological wound healing process in response to chronic injury. It is characterized by excessive extracellular matrix production and accumulation, which eventually affects organ architecture and results in organ failure. Fibrosis can affect a wide range of organs, including the heart and lungs, and have limited therapeutic options. DNA methylation, like other epigenetic process, is reversible, therefore regarded as attractive therapeutic interventions. Although epigenetic mechanisms are highly interactive and often reinforcing, this review discusses DNA methylation-dependent mechanisms in the pathogenesis of organ fibrosis, with focus on cardiac and pulmonary fibrosis. We discuss specific pro- and anti-fibrotic genes and pathways regulated by DNA methylation in organ fibrosis; we further highlight the potential benefits and side-effects of epigenetic therapies in fibrotic disorders.
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