| Project/Area Number |
16K19909
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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 |
Digestive surgery
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Research Collaborator |
ICHINOHE Daichi
KIMURA Norihisa
MIURA Takuya
MOROHASHI Satoko
TSUTSUMI Shinji
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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 |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 肝線維化 / 肝移植 / 肝星細胞 / 免疫抑制剤 / 線維化 / コラーゲン合成 / 合併症 / 肝硬変 |
|---|
| Outline of Final Research Achievements |
A critical complication of liver transplantation (LT) is development of liver fibrosis, which can lead to worse long-term graft and patient survival as well as potential need for re-transplantation. To assess liver fibrosis following LT, we thought it was reasonable to focus on hepatic stellate cells (HSC) which have a central role in liver fibrosis. The purpose of this study was to clarify the effect of immunosuppressive drugs (IS) on HSC for the development of the anti-fibrosis strategy in patients after LT. As a result, we have discovered 1) IS can inhibit the activation of quiescent HSC to the activated form, 2) IS can suppress the collagen synthesis in HSC, 3) IS do not suppress the total function of activated HSC, but can selectively suppress specific functions of them. Our results have a significant contribution to establishing the anti-fibrosis strategy in patients after LT.
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| Academic Significance and Societal Importance of the Research Achievements |
肝移植医療の発展はめざましく長期生存症例が増加する一方で、様々な晩期合併症が明らかになってきた。晩期合併症の一つである移植肝の線維化は、移植肝不全に至る重大な病態であり、より良い肝移植後生活のために、その対策は必須である。
本研究は、免疫抑制剤により、肝線維化過程において中心的役割を担う肝星細胞の活性化や機能を制御できる可能性を示唆した。この結果は、移植肝の線維化予防および治療戦略の確立に貢献しうるものであり、肝移植医療において大きな意義があることと思われる。
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