A multi-organ linkage approach to the pathogenesis of disease in human like NASH model mice
| Project/Area Number |
17K08781
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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 |
Experimental pathology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Warabi Eiji 筑波大学, 医学医療系, 講師 (70396612)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | NASH |
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| Outline of Final Research Achievements |
Nonalcoholic steatohepatitis (NASH) is a fatal disease caused by the accumulation of fat, mainly triglycerides, in hepatocytes, resulting in inflammation and fibrosis. In the present study, we analyzed the pathogenesis of NASH in spontaneously developing p62 and Nrf2 double-deleted (DKO) mice. The results showed that the increased percentage of gram-negative bacteria in DKO mice compared to wild-type mice, high levels of inflammatory metabolites in the feces, decreased intestinal barrier function, and decreased phagocytosis of hepatic kupffer cells were deeply involved in the disease. It was suggested that Nrf2 deficiency was a major factor in these causes.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦では200万人以上のNASH罹患者がいると推定され、今後も増大することが予想されており、その対策が社会的急務となっている。NASH患者には肥満・糖尿病・脂質異常症などを持つ人が多く、生活習慣病を背景に発症するものと考えられているが、詳細な機序は不明である。また、治療は食生活の改善、運動療法が有効であるが、根本的な治療法、治療薬は存在しない。本研究は、代表者らが新たに開発したヒトNASHと類似した病態を呈するマウスモデルを用いて、NASH発症機序を解析した。得られた成果は、NASHの予防、治療に有用な知見となる。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Association between p62 expression and clinicopathological characteristics in oral leukoplakia.2019
Author(s)
T. Yoshida, T. Terabe, H. Nagai, F. Uchida, S. Hasegawa, T. Nagao, S. Miyabe, N. Ishibashi‐Kanno, K. Yamagata, E. Warabi, M. Gosho, T. Yanagawa, H. Bukawa
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Journal Title
Clinical and Experimental Dental Research
Volume: 5
Issue: 4
Pages: 389-397
DOI
NAID
Related Report
Peer Reviewed / Open Access
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