| Project/Area Number |
17H02177
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | メタボリック症候群 / 非アルコール性脂肪肝炎 / 肝硬変 / 肝癌 / サイトカイン |
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| Outline of Final Research Achievements |
Nonalcoholic steatohepatitis (NASH) is characterized by the presence of hepatocyte injury and inflammation in addition to steatosis, and can progress to more severe liver diseases, including cirrhosis and hepatocellular carcinoma. However, the mechanisms underlying the progression from simple steatosis to NASH are not fully understood. We demonstrated that methionine- and choline-deficient (MCD) diet-induced liver injury and inflammation were aggravated in oncostatin M (OSM)-deficient mice compared to those in wild-type mice. In addition, treatment with OSM ameliorated liver injury and inflammation in ob/ob mice fed MCD diet. Furthermore, OSM suppressed the progression from NASH to hepatocellular carcinoma (HCC) in STAM model. From these findings, OSM may be a novel cytokine that modulates liver injury and inflammation in NASH, and such effects of OSM leads to the suppression of HCC development.
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| Academic Significance and Societal Importance of the Research Achievements |
NAFLDの増悪におけるNASH-肝硬変-肝癌の代謝性肝疾患悪性化シークエンスは炎症、線維化、癌化の過程が時間的に重複して進行していくため、各過程を個別に抑制するだけでは有効な治療効果は得られず、これらの過程を同時に抑制することが重要であると考えられる。本研究により、OSMはNAFLからNASHの進行における肝障害や炎症の抑制作用を有すること、また、NASHを基盤とした肝癌の発症を抑制することが明らかとなった。以前の研究で、OSMはNAFLの抑制効果も認めていることより、代謝性肝疾患悪性化シークエンスに対して複数の作用を有するOSMは、同疾患群に対する新規治療薬の候補となる可能性が考えられる。
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