| Project/Area Number |
18K07976
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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 53010:Gastroenterology-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
Ido Akio 鹿児島大学, 医歯学域医学系, 教授 (30291545)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | マクロファージ / 形質転換 / 肝細胞増殖因子 / 肝再生 / M1 マクロファージ / M2 マクロファージ / 修復 / 急性冠不全 / gpnmb / 肝硬変 / 急性肝不全 / 肝障害 / 肝繊維化 |
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| Outline of Final Research Achievements |
Macrophages are innate immune cells involved in homeostasis, the immune response, inflammation, regeneration, and the resolution of inflammation in tissues. Macrophage polarization states are mainly divided into two types, the pro-inflammatory or classically activated M1 phenotype and the anti-inflammatory or alternatively activated M2 phenotype. In this study, we investigated the effect of HGF on macrophage phenotype using mouse bone marrow-derived macrophages. HGF specific receptor, c-Met, was expressed in M1 macrophages polarized by treatment with interferon-r and LPS. Treatment with HGF induced expression of Arg-1 mRNA and secretion of IL-10 and TGF-beta, and decreased iNOS expression through PI3K pathway. Additionally, HGF treatment sifted the M1 macrophage intracellular metabolism toward an M2 phenotype, especially with respect to fatty acid metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
傷害組織の修復過程において、組織修復マクロファージが重要な役割を果たしている。HGFは肝再生を強力に促進する増殖因子であるが、種々の組織の傷害組織の再生・修復における重要な液性因子である。本研究では、組織傷害時に浸潤した炎症性（M1）マクロファージが、組織の修復過程において抗炎症性（M2）マクロファージに形質転換にHGFが関与していることを明らかにした。HGFが、細胞増殖や細胞遊走といった上皮系細胞への作用に加えて、組織修復の微笑環境で重要な役割を果たしているマクロファージに対しても炎症から抗炎症、組織修復に関わる形質転換を誘導することが明らかになり興味深い。
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