Analysis of the molecular mechanism of hepatic fibrosis initiating from lipid peroxidation of lipid-soluble signaling molecules
| Project/Area Number |
16K08721
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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 | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | lipid peroxidation / lipid peroxide / protein kinase c / diacylglycerol / liver fibrosis / oxidative stress / ｍass spectrometry / hepatic stellate cell / mass spectrometry / プロテインキナーゼC / ジアシルグリセロール / 細胞内シグナル伝達 / 肝線維化 / 四塩化炭素 / Protein kinase c / Diacylglycerol / Lipid peroxide / Lipid peroxidation / Liver fibrosis / 細胞傷害 / 肝線維症 / 脂質過酸化 |
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| Outline of Final Research Achievements |
We analyzed the molecular mechanism of liver fibrosis starting from peroxidized DAG. Peroxidized DAG was significantly increased in mouse liver tissue in which liver fibrosis was induced by carbon tetrachloride administration. In addition, the administration of Ebselen, which has the ability to reduce and eliminate peroxidized DAG, suppressed the increase in peroxidized DAG and improved the liver fibrosis. When peroxidized DAG was applied to primary-cultured cells of mouse hepatic stellate cells, the hepatic stellate cells were activated and changed into myofibroblast-like cells. From the above results, it was clarified that peroxidized DAG produced by oxidative stress acts as a key molecule in liver fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、これまで漠然とした傷害作用として捉えられてきた酸化ストレス傷害を、特定の機能性脂質分子（DAG）の過酸化による特定のPKCアイソザイムの活性化と情報伝達異常、さらにはこれに対応する酸化ストレスシグナル抑制分子による制御応答といった分子レベルでの理解を可能とし、本研究で対象としている肝線維化疾患ばかりでなく、酸化ストレスが関与するとされる、アルツハイマー病、パーキンソン病などの神経変性疾患、動脈硬化症、虚血―再疎通疾患などの種々の疾患の病因の厳密な追求、解明を行う際の重要な拠点となるものと思われる。
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Report
(5 results)
Research Products
(32 results)
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[Journal Article] Nanometer-Scale Structures of Neurons Differ Between Individuals and Those Differences Become Extraordinary in Schizophrenia2019
Author(s)
Rino Saiga(筆頭者) Vincent De Andrade Francesco De Carlo Akihisa Takeuchi Kentaro Uesugi Y Terada, Y Suzuki, S Takekoshi, C Inomoto, N Nakamura, Y Torii, I Kushima, S Iritani, N Ozaki, K Oshima, M Itokawa, M Arai, RMizutani
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Journal Title
Microscopy and Microanalysis
Volume: 25
Issue: S2
Pages: 1344-1345
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Three-dimensional alteration of neurites in schizophrenia.2019
Author(s)
Mizutani R, Saiga R, Takeuchi A, Uesugi K, Terada Y, Suzuki Y, De Andrade V, De Carlo F, Takekoshi S, Inomoto C, Nakamura N, Kushima I, Iritani S, Ozaki N, Ide S, Ikeda K, Oshima K, Itokawa M, Arai M.
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Journal Title
Transl Psychiatry.
Volume: 9
Issue: 1
Pages: 1-12
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pathophysiological characteristics of non-alcoholic steatohepatitis-like changes in cholesterol-loaded type 2 diabetic rats.2018
Author(s)
Toriniwa Y, Muramatsu M, Ishii Y, Riya E, Miyajima K, Ohshida S, Kitatani K, Takekoshi S, Matsui T, Kume S, Yamada T, Ohta T.
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Journal Title
Physiol Res.
Volume: 67
Pages: 601-612
Related Report
Peer Reviewed / Open Access
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[Journal Article] Determination of triacylglycerol oxidation mechanisms in canola oil using liquid chromatography-tandem mass spectrometry.2018
Author(s)
Kato S, Shimizu N, Hanzawa Y, Otoki Y, Ito J, Kimura F, Takekoshi S, Sakaino M, Sano T, Eitsuka T, Miyazawa T, Nakagawa K.
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Journal Title
Science of Food
Volume: -
Issue: 1
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
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