| Project/Area Number |
25282212
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Applied health science
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Mizogami Yuji 筑波大学, 医学医療系, 准教授 (70268556)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGAWA Toru 筑波大学, 医学医療系, 准教授 (10312852)
UTSUNOMIYA Hirotoshi 和歌山県立医科大学, 共同利用施設, 准教授 (60264876)
ISOBE Tomonori 筑波大学, 医学医療系, 准教授 (70383643)
WARABI Eiji 筑波大学, 医学医療系, 講師 (70396612)
SHODA Junichi 筑波大学, 医学医療系, 教授 (90241827)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2015: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2013: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
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| Keywords | 肥満 / 非アルコール性脂肪性肝炎 / 遺伝子改変マウス / リポ多糖 / Kupffer細胞 / 生活習慣病 / 過食肥満マウス / 脂肪性肝炎 / 腸内細菌叢 / 自然免疫 / NASH |
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| Outline of Final Research Achievements |
Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that develops from simple steatosis to liver cirrhosis and hepatocellular carcinoma. Effective prevention and treatment methods are strongly desired. We generated double knockout (DKO) mice without Sqstm1 and Nrf2 genes. In DKO mice, a number of biological molecules from the intestine and adipose tissue in addition to liver may play central roles in the onset of NASH. The serum LPS levels were significantly higher in DKO mice than that in WT mice. Furthermore, the intestinal permeability and the gram-negative bacteria levels and endotoxin in feces were all increased significantly in DKO mice. DKO mice had a significant decrease in Kupffer cells (KCs)’ phagocytic function. The overload of serum LPS induced by the modification of intestine microbiota, the increase of intestinal permeability, and the impaired clearance of LPS by KCs dysfunction were considered to be important for the progression of NASH in DKO mice.
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