| Project/Area Number |
18K08194
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
Hirata Yutaka 兵庫医科大学, 医学部, 講師 (10441247)
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| Co-Investigator(Kenkyū-buntansha) |
松本 久子 京都大学, 医学研究科, 准教授 (60359809)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 喘息 / IL-33 / YKL-40 / PAR-2 / miRNA / 気道上皮細胞 |
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| Outline of Final Research Achievements |
IL-33 is markedly increased in severe asthma and plays a central role in the onset, but its pathological production mechanism remains unclear. In this study, constitutive IL-33 expression in airway epithelial cells was attenuated by purified YKL-40 and YKL-40 overexpression. On the other hand, IL-33 expression was significantly increased in cell lines in which YKL-40 expression was suppressed. Furthermore, the increase in IL-33 expression induced by Alternaria (AA) was significantly reduced in the YKL-40 overexpressing cell line. On the other hand, in the PAR-2 expression-suppressed cell line, the expression of IL-33 was significantly increased. Therefore, a mechanism mediated by PAR-2 was suggested as a mechanism by which YKL-40 suppresses IL-33 expression.
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| Academic Significance and Societal Importance of the Research Achievements |
YKL-40は喘息患者の喀痰中濃度が重症度、気道リモデリング、非2型気道炎症と相関し、疫学コホート研究から、YKL-40は非2型・好中球性喘息のバイオマーカーとして注目されており、本研究で見出されたYKL-40によるPAR-2を介したIL-33発現制御のメカニズムは、喘息のステロイド低感受性における難治化に対する治療薬開発の新たなアプローチとなるだけでなく、2型・非2型炎症の調整機構の解明の糸口になると共に、個別化治療などの臨床応用に貢献する意義がある。
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