| Project/Area Number |
17K15933
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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 | Kanazawa University |
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Principal Investigator |
Okada Hikari 金沢大学, 医学系, 博士研究員 (50788916)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | ペレチノイン / オートファジー / 慢性炎症 / 発癌 / 肝線維化 / Atg16L1 / CEBPα / オートファージー / 線維化 / 再発 |
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| Outline of Final Research Achievements |
The pathogenesis of non-alcoholic steatohepatitis (NASH) is still unclear and the prevention of the development of hepatocellular carcinoma (HCC) has not been established. We found that peretinoin induced autophagy in the liver of mice, which was characterized by the increased co-localized expression of LC3B-II and Lamp2, and increased autophagosome formation and autophagy flux in the liver. Especially, Atg16L1 was repressed at both the mRNA and protein level. Decreased Atg16L1 mRNA expression was also found in the liver of patients with NASH according to disease progression. Interestingly, Atg16L1 overexpression in HepG2 cells inhibited palmitate-induced NF-kB activation and IL6/ STAT3 activation. We showed that Atg16L1 induced the de-phosphorylation of Gp130, a receptor subunit of interleukin-6 family cytokines, which subsequently repressed phosphorylated STAT3 (Tyr705) levels, and this process might be independent of autophagy function.
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| Academic Significance and Societal Importance of the Research Achievements |
1）NASH、肝線維化、肝発がんの影響を、実臨床に即した発がんモデルで解析を行うことで臨床応用に貢献できる。2）ウイルス、腸内細菌、肥満を背景とした肝疾患病態進行による肝組織内のATG16L1 発現回復は、慢性炎症を抑制し、肝線維化の進行や肝細胞癌の再発に対する新規治療標的になり得る可能性がある。Atg16L1 の分子メカニズムを解明は、肝細胞癌の再発率および生存率の改善に貢献できる。
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