Suppression of obesity- and NASH-related liver carcinogenesis by regulating hypertension and renin-angiotensin system
| Project/Area Number |
16K19335
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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 | Gifu University |
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Principal Investigator |
Kochi Takahiro 岐阜大学, 大学院医学系研究科, 非常勤講師 (00444282)
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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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | NASH / 肝発癌 / 肥満 / 高血圧 / 肝線維化 / Hypertension / Renin-Angiotensin System |
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| Outline of Final Research Achievements |
Using rats exhibiting hypertension, obesity and diabetes, an animal model reflecting human metabolic syndrome was newly created, characterized by the promotion of renin-angiotensin system (RAS). In addition to presenting liver histopathology similar to human NASH, this model was also confirmed to show liver fibrosis and liver precancerous lesions by high-fat diet and carbon tetrachloride. Administration of green tea catechins suppressed liver fibrosis and hepatic carcinogenesis, suppressed RAS signaling in the liver, and reduced oxidative stress markers. It was suggested that regulation of RAS and oxidative stress leads to suppression of metabolic syndrome-related hepatic fibrosis and liver carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
肥満や糖尿病、高血圧をはじめとする生活習慣病の増加は大きな社会問題であり、これらの疾患を合併した慢性肝疾患患者の増加が危惧される。また、NASHに関連した肝細胞癌の更なる増加も予想される。本研究によって、レニン-アンギオテンシン系および酸化ストレスの制御が、メタボリック症候群およびNASHに関連する肝線維化・肝発癌の抑制に繋がることが示唆された。既存あるいは新規の薬剤によって上記の病態を制御することで、肝発癌および肝癌再発のリスクの高い肥満や糖尿病を合併した慢性肝疾患患者、さらにはNASH患者の予後改善が期待できる。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Non-alcoholic steatohepatitis-related liver tumorigenesis is suppressed in mice lacking hepatic retinoid storage2017
Author(s)
Ideta, T. Shirakami, Y. Ohnishi, M. Maruta, A. Obara, K. Miyazaki, T. Kochi, T. Sakai, H. Tomita, H. Tanaka, T. Blaner, W. S. Shimizu, M.
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Journal Title
Oncotarget
Volume: 8
Issue: 41
Pages: 70695-70706
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Preventative Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice2017
Author(s)
Fukuta K, Shirakami Y, Maruta A, Obara K, Iritani S, Nakamura N, Kochi T, Kubota M, Sakai H, Tanaka T, Shimizu M
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Journal Title
Int J Mol Sci
Volume: 18(2)
Issue: 2
Pages: 413-413
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis.2015
Author(s)
Hanai T, Shiraki M, Ohnishi S, Miyazaki T, Ideta T, Kochi T, Imai K, Suetsugu A, Takai K, Moriwaki H, Shimizu M.
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Journal Title
Hepatol Res
Volume: 印刷中
Issue: 8
Pages: 743-751
DOI
Related Report
Peer Reviewed
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