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Abstract
Nasal polyposis is a multi-factorial disease associated with chronic inflammation of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. Epigenetics, DNA methylation, and chromatin modifications are critical for generating cellular diversity and for maintaining distinct gene expression profiles. Based on our recent study that evaluated the inhibitory effect of Trichostatin A on myofibroblast differentiation in nasal polyposis, we hypothesized that HDAC inhibition is associated with myofibroblast differentiation and extracellular matrix accumulation in nasal polyposis and suggested that Trischostatin A may be useful as an inhibitor of nasal polyp growth and thus has potential to be used as a novel treatment option for nasal polyposis. In this review, we present general concept of epigenetics and results of recent research that elucidate the role of epigenetics in the pathogenesis of nasal polyps.
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Fig. 1
Schematic of DNA methylation and histone modification. DNA is methylated exclusively at cytosines at CpG dinucleotides.
Fig. 2
Schematic of the reversible changes in chromatin organization that influence gene expression by histone acetylation or DNA methylation: genes are expressed (switched on) when the chromatin is open (active), and they are inactivated (switched off) when the chromatin is condensed (silent). White circles=un-methylated cytosines; red circles=methylated cytosines; green curved line=Histone acetylation.
Fig. 3
Effect of trichostatin A (TSA) on myofibroblast differentiation and extracelluar matrix (ECM) production in transforming growth factor (TGF)-b1-induced nasal fibroblasts. (A) Semi-quantitative RT-PCR of a-smooth muscle actin (a-SMA) mRNA transcript (B) quantitative analysis of a-SMA mRNA transcript (C) western blot of a-SMA protein (D) immunofluorescent staining of a-SMA protein expression was determined. (E) Collagen type I mRNA transcript was examined by semi-quantitative RT-PCR and (F) total collagen was measured with Sircol assay kit. (G-H) Contractile activity was assessed by collagen gel contraction assay and the contraction area was measured. Asterisks (∗: p＜0.05, ∗∗: p＜0.01) indicate statistically significant difference. The results are obtained from at least three independent experiments. Scale bar, 100 μm.
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