| Project/Area Number |
17K08322
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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 |
Pharmacology in pharmacy
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| Research Institution | Kyoto Pharmaceutical University |
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Principal Investigator |
Akiba Satoshi 京都薬科大学, 薬学部, 教授 (70231826)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脂肪肝炎 / 炎症 / ホスホリパーゼA2 |
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| Outline of Final Research Achievements |
Non-alcoholic steatohepatitis (NASH) is characterized by hepatic fibrosis with inflammation. However, effective pharmacotherapeutic strategies for hepatic fibrosis in NASH remain to be established. Among the initiators of inflammation, we have been investigating the possible involvement of group IVA phospholipase A2 (IVA-PLA2), which catalyzes the initial step of the generation of lipid mediators, in the progression of hepatic fibrosis. We showed that a lack of IVA-PLA2 alleviates hepatic fibrosis in NASH model mice, suggesting the contribution of IVA-PLA2-mediated cellular responses. We further explored which types of cells in the liver are involved in IVA-PLA2-mediated hepatic fibrosis using cell-specific IVA-PLA2 knockout mice. The preliminary results suggest that IVA-PLA2 in endothelial cells plays a role, in part, in the hepatic stellate cell-mediated progression of hepatic fibrosis. Thus, IVA-PLA2 may be a pharmacotherapeutic target for NASH.
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| Academic Significance and Societal Importance of the Research Achievements |
非アルコール性脂肪肝炎は、肝線維化を伴う生活習慣病であり、死因となる肝硬変や肝癌へと移行するが、未だ効果的な治療薬はない。本研究は、炎症の制御が治療に繋がると考え，炎症を担うIVA型ホスホリパーゼA2（IVA-PLA2）という酵素のはたらきを止めることが新規の治療方針となる可能性を示した。肝臓の全ての種類の細胞中のIVA-PLA2のはたらきを止めなくても、肝臓の血管を構成する細胞のIVA-PLA2だけを抑制する治療薬があれば、副作用が少ない安全な肝線維化の治療薬となることが予想された。
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