| Project/Area Number |
16K19382
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Yoshio Sachiyo 国立研究開発法人国立国際医療研究センター, その他部局等, 肝疾患先端治療研究室長 (10774060)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | キヌレニン / NAFLD / 肝線維芽細胞 / IL-34 / YKL-40 / 肝線維化 / 免疫能低下 / IDO / 線維芽細胞 / Natural Killer 細胞 / 免疫学 / 細胞・組織 / ウィルス / 生態学 |
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| Outline of Final Research Achievements |
Serum levels of IL-34 and YKL-40 increased with the progression of liver fibrosis in NAFLD patients. The levels of serum kynurenie were also high in NAFLD patients with advanced fibrosis. Primary liver fibroblasts were obtained from surgical resections of non-cancerous liver from NAFLD patients. Primary fibroblasts produced IL-34 and kynurenine. The addition of kynurenin or the agonist of AhR, the receptor of kynurenine, upregulated the expression levels of ACTA2, TIMP1 and COL1A1 in primary fibroblasts. Upregulation of kynurenine pathway might exacerbate liver fibrosis though activating fibroblasts.
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪性肝疾患（NAFLD)は、世界的にも国内でもその患者数が近年増加しています。肝臓の慢性的な炎症が続くことにより、肝臓に線維化がすすみ、肝硬変・肝がんが発症することがあります。この研究により、NAFLD患者において、トリプトファン代謝経路が亢進しキヌレニンがたくさん産生されることがその線維化を悪化させる一因である可能性が示されました。今後、治療標的として期待されます。
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