| Project/Area Number |
18K15994
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 腹膜線維化 / マイクロRNA / 腹膜透析 / マクロファージ |
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| Outline of Final Research Achievements |
In this study, treatment by GLP-1 receptor agonist Exendin-4 (Ex-4) ameliorated the production of inflammatory cytokines from M1 macrophages differentiated from THP-1 cells in vitro. Also, Ex-4 improved peritoneal fibrosis and reduced mRNA expressions such as PAI-1 and inflammatory cytokine in the peritoneal tissue of the peritoneal fibrosis model mice. These protective effects by Ex-4 were expected to be mediated via the GLP-1 receptor expressed on the surface of macrophages. Therefore, we focused on the mechanism through the change in expressions of microRNAs contained in the macrophage-derived exosomes. However, we have not yet identified microRNAs which show significant changes by Ex-4 treatment. Further investigation is needed to be continued to identify specific microRNA, contained in the macrophage-derived exosome, that mediates protective effect of Ex-4 against peritoneal fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病治療薬としても使用されているGLP-1受容体アゴニストが、腹膜透析の長期的弊害の一つである腹膜線維化を抑制する可能性が示唆され、腹膜透析の長期継続や腹膜線維化抑制の新規薬剤開発に貢献できる可能性がある。これがマクロファージ由来エクソソームに内在する特定のマイクロRNAを介した作用であることを示せれば、組織線維化をもたらす炎症性疾患の制御に幅広く応用できる可能性があり、今後検討を継続したい。
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