| Project/Area Number |
18K15827
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Chiba University |
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Principal Investigator |
Nakagawa Ryo 千葉大学, 大学院医学研究院, 特任講師 (60594596)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | T細胞 / N-Ras / 免疫制御 / CD4+T細胞 / N-Ras阻害剤 / 原発性胆汁性胆管炎 / Ras阻害剤 / スクリーニング / 原発泳胆汁性肝硬変 / IFN-γ |
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| Outline of Final Research Achievements |
We have been analyzing the immunokinetics of primary biliary cholangitis (PBC) using molecular biological techniques. We have shown that PBC is associated with increased T cell activation and Th1 cytokine production, mainly IFN-γ, accompanied by increased N-Ras expression. And it was shown that N-Ras could be an immunoregulatory molecule for PBCs. However, the universality and specificity of the pathological relationship between PBC and N-Ras expression have not been fully analyzed. Therefore, we confirmed the reproducibility of N-Ras expression in PBCs. In addition, we compared the inhibitory effect of Ras inhibitors on Th1 cytokine production in order to select candidate drugs for the treatment of PBC. This study clarified a part of the pathogenesis of PBC and established the basis for a new therapeutic approach.
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| Academic Significance and Societal Importance of the Research Achievements |
難病であるPBCの病態の一端を解明し、それに基づいた新たな治療法を提唱した。PBCは自己免疫性疾患にも胆汁うっ滞を改善させるための治療しか存在しない。本研究によりTas阻害剤を用いることでPBCの免疫治療が開発できる可能性を示す事ができた。これにより従来の治療法に抵抗性を示す症例に対して、治療アプローチをすることが可能となる。また、免疫動態を正常化させることで、PBCを寛解させる事ができる可能性もある。そのため、本研究の社会的意義は大きいと考える。
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