| Project/Area Number |
15K10792
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Toho University |
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Principal Investigator |
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| Research Collaborator |
MATSUMOTO Kenji
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 慢性副鼻腔炎 / マイクロアレイ / フェノタイプ / エンドタイプ / エピジェネティクス / Phenotype / Endotype / phenotype / endotype / DNAマイクロアレイ |
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| Outline of Final Research Achievements |
Hierarchical clustering and principal component analysis (PCA) collectively showed that eosinophilic chronic rhinosisusitis with nasal polyps (ECRSwNP) and non-ECRSwNP (NECRSwNP) had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (IL4, IL5, and CSF2) reported so far, but also cell cycle regulators (CDKNA1 and CCND1) and a tissue fibrosis-related molecule (TGF-β) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP. These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.
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| Academic Significance and Societal Importance of the Research Achievements |
好酸球性副鼻腔炎や非好酸球性副鼻腔炎などのフェノタイプとは関係のない,治療抵抗性に関するエンドタイプを同定することにより,これまで報告されてきた好酸球に関連する因子以外の難治化因子が明らかとなった.その結果,既存の治療に抵抗性の慢性副鼻腔炎に対する,新規治療の開発や創薬に繋がることが期待される.また,慢性副鼻腔炎患者の術後の予後とDNAマイクロアレイによる鼻組織の網羅的遺伝子発現解析をもとにした病態のエンドタイプ分類は,慢性副鼻腔炎全体の治癒率の向上に貢献する.
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