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The Role of Epigenetics in the Chronic Sinusitis with Nasal Polyp
Tiancong Liu1, Yang Sun1, Weiliang Bai2
1Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Purpose Of Review:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and heterogeneous inflammatory disease. The underlying epigenetic mechanisms and treatment of CRSwNP are partially understood. Of the different epigenetic changes in CRSwNP, histone deacetylases (HDACs), methylation of DNA, and the levels of miRNA are widely studied. Here, we review the human studies of epigenetic mechanisms in CRSwNP.
Recent Findings:
The promoters of COL18A1, PTGES, PLAT, and TSLP genes are hypermethylated in CRSwNP compared with those of controls, while the promoters of PGDS, ALOX5AP, LTB4R, IL-8, and FZD5 genes are hypomethylated in CRSwNP. Promoter hypermethylation suppresses the gene expression, while promoter hypomethylation increases the gene expression. Studies have shown the elevation in the levels of HDAC2, HDAC4, and H3K4me3 in CRSwNP. In CRSwNP patients, there is also an upregulation of certain miRNAs including miR-125b, miR-155, miR-19a, miR-142-3p, and miR-21 and downregulation of miR-4492. Epigenetics takes part in the immunology of CRSwNP and may give rise to endotypes of CRSwNP. Both HDAC2 and the miRNA including miR-18a, miR-124a, and miR-142-3p may take function in the regulation of glucocorticoid resistance. HDAC inhibitors and KDM2B have shown effectiveness in decreasing nasal polyp, and DNA methyltransferase (DNMT) or HDAC inhibitors may have a potential efficacy for the treatment of CRSwNP. Recent advances in the epigenetics of CRSwNP have led to the identification of several potential therapeutic targets for this disease. The use of epigenetics may provide novel and effective biomarkers and therapies for the treatment of nasal polyp.
Insights
Epigenetic changes like DNA methylation and microRNA (miRNA) levels are key in chronic rhinosinusitis with nasal polyps (CRSwNP). These mechanisms offer potential new treatments and biomarkers for CRSwNP.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex inflammatory condition with incompletely understood epigenetic underpinnings.
- Epigenetic modifications, including DNA methylation, histone deacetylases (HDACs), and microRNAs (miRNAs), are increasingly recognized as crucial in CRSwNP pathogenesis.
Purpose of the Study:
- To review human studies investigating the role of epigenetic mechanisms in CRSwNP.
- To explore the potential of epigenetic targets for novel CRSwNP therapies and biomarkers.
Main Methods:
- Review of human studies on epigenetic mechanisms in CRSwNP.
- Analysis of gene promoter methylation patterns (hyper- and hypomethylation).
- Examination of histone deacetylase (HDAC) levels and histone modifications.
- Assessment of microRNA (miRNA) expression profiles.
Main Results:
- CRSwNP exhibits altered DNA methylation in specific genes (e.g., COL18A1, PTGES, PGDS, ALOX5AP).
- Elevated levels of HDAC2, HDAC4, and H3K4me3, along with dysregulated miRNA expression (e.g., miR-125b, miR-155, miR-4492), are observed in CRSwNP.
- Epigenetic factors, including HDAC2 and specific miRNAs, are implicated in glucocorticoid resistance.
- HDAC inhibitors and KDM2B show promise in reducing nasal polyps, suggesting therapeutic potential for DNMT or HDAC inhibitors in CRSwNP treatment.
Conclusions:
- Epigenetic alterations play a significant role in CRSwNP immunology and may define disease endotypes.
- Epigenetic modifications represent promising targets for developing novel therapeutic strategies and biomarkers for CRSwNP.
- Targeting epigenetic mechanisms offers a potential avenue for improving treatment outcomes and managing glucocorticoid resistance in CRSwNP.
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