2023 Fiscal Year Final Research Report
Mechanism Elucidation of Initial Activation of Hepatic Stellate Cells and Application to Sinusoid Reconstruction and Artificial Liver
| Project/Area Number |
21K06757
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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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| Review Section |
Basic Section 48010:Anatomy-related
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| Research Institution | Osaka Metropolitan University (2022-2023)
Osaka City University (2021) |
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Principal Investigator |
Ikeda Kazuo 大阪公立大学, 大学院医学研究科, 教授 (80275247)
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| Co-Investigator(Kenkyū-buntansha) |
松原 勤 大阪公立大学, 大学院医学研究科, 准教授 (20628698)
宇留島 隼人 大阪公立大学, 大学院医学研究科, 講師 (90755745)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 肝星細胞 / 肝類洞再構築 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop a culture system that mimics the liver tissue environment and can maintain quiescent hepatic stellate cells (HSCs). This system was used to elucidate the mechanisms that trigger the initial activation of HSCs, which are responsible for liver fibrosis. During the research period, we clarified that HSCs and hepatocytes construct adherens junctions via E-cadherin. Additionally, we discovered a novel activation mechanism in which the loss of these adherens junctions due to hepatocyte necrosis during liver injury leads to the activation of the YAP/TAZ pathway in HSCs, contributing to their initial activation. To achieve more detailed observation of the microenvironment, we successfully used three-dimensional reconstruction of serial section images obtained through transmission electron microscopy to observe the morphology of HSCs in both normal and inflamed livers, revealing significant morphological differences.
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| Free Research Field |
分子解剖学
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| Academic Significance and Societal Importance of the Research Achievements |
一般的な肝星細胞活性抑制研究はすでにinitiationからperpetuationへ移行した段階での活性抑制を目指した研究である。未だ有効な肝星細胞活性抑制剤が開発されていないことは、肝星細胞の活性抑制はinitiationをターゲットとする必要があると言える。本研究期間で我々が開発した、E－カドヘリンを介した接着結合を再現した培養法を用いればinitiationの研究を行うことができ、新たな肝星細胞活性抑制剤候補分子の創出を介して、肝硬変の治療へ貢献することが期待できる。また本研究によって肝類洞構造の一端が解明できたので、将来的な人工肝の開発に重要な基礎データを集積できたと考えられる。
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