| Project/Area Number |
15K12698
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied health science
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| Research Institution | Kanazawa University |
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Principal Investigator |
Ota Tsuguhito 金沢大学, 脳・肝インターフェースメディシン研究センター, 准教授 (60397213)
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 機能性脂質 / スフィンゴシンキナーゼ / 非アルコール性脂肪肝炎 / 肝がん / スフィンゴシン１リン酸 |
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| Outline of Final Research Achievements |
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. Ectopic fat or lipotoxicity in the liver can cause NASH-associated hepatocellular carcinoma (HCC). However, its underlying mechanism is unclear. In this study, we studied the role of a functional bioactive lipid ‘S1P’and its rate-limiting enzyme sphingosine kinase (SphK) in the development of NASH-associated HCC. We found that SphK activity and mRNA expression increased in the liver of both NASH mice and NASH patients compared those in normal liver. By contrast, knockdown of SphK led to suppress HCC development in hepatoma cell lines. Moreover, we found that diet or chemical-induced carcinogenesis in the liver were significantly decreased in SphK knockout mice compared to that in control mice. Thus, SphK might be a novel therapeutic target of NASH-associated HCCs.
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