| Project/Area Number |
17K09014
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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 |
Laboratory medicine
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
谷 丈二 香川大学, 医学部, 助教 (00596075)
正木 勉 香川大学, 医学部, 教授 (30335848)
藤田 浩二 香川大学, 医学部附属病院, 助教 (50749421)
野村 貴子 香川大学, 医学部, 協力研究員 (70645415)
米山 弘人 香川大学, 医学部附属病院, 助教 (80294750)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 非アルコール性脂肪性肝炎 / マイクロRNA / ガレクチン９ / ガレクチン9 / 分子生物学 / トランスレーショナルリサーチ |
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| Outline of Final Research Achievements |
We confirmed the efficacy of Galectin-9 in inhibiting NASH progression, carcinogenesis and proliferation in STAM mice and galectin-9-deficient STAM mice. We also identified targetable microRNAs that were significantly expressed in Galectin 9-deficient STAM mice as compared to STAM mice. By analyzing the significantly variable microRNAs obtained from human and mouse samples, common microRNAs were extracted and real targetable microRNAs were identified. In addition, LPS was administered to bone marrow-derived macrophages from Wild type and Galectin 9-deficient mice in the presence of leptin. CD14 and TNFα were measured in the culture medium. The macrophages from Galectin 9-deficient mice demonstrated a marked increase. Therefore, we found that it is important to regulate the secretion of Galectin-9 in M2-like macrophages, which play an important role in the improvement of NASH, and targetable microRNAs involved in NASH development were identified.
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| Academic Significance and Societal Importance of the Research Achievements |
NASH進展からの発癌抑制効果のあるガレクチン9（作用機序はTim-3を経由することしか明らかでない）を制御するマイクロRNAの網羅的な発現プロファイリングを作成することは、治療の困難なNASHに対する抗炎症効果、あるいはNASHからの発癌および増殖抑制効果の可能性、さらにはNASH発癌の新たなマーカー、および治療法の発見につながることが期待される。将来的には、NASHのみならず、さまざまな糖脂質代謝性疾患の診断、治療、創薬開発を目指したバイオ産業の基盤技術となる可能性を秘めている。
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