| Project/Area Number |
18K14655
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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 43030:Functional biochemistry-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Fujihira Haruhiko 順天堂大学, 医学(系)研究科(研究院), 特任助教 (50721057)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | Ngly1 / Nfe2l1 / マウス造血発生 / 糖鎖脱離酵素 / 細胞質における糖鎖分解 / 造血発生 / NEF2L1 (Nrf1) |
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| Outline of Final Research Achievements |
The purpose of this study is “Revealing the physiological role of Ngly1 on the murine hematopoiesis”. To this end, I analyzed embryonic liver and blood cells at the several time points of gestation. As a result, I found that the enucleation of erythroblast, which is known to occur along with the maturation of red blood cells, was significantly decreased in Ngly1-KO blood cells. I also found that the development of liver, which is judged by the staining intensity of AFP, was slightly delayed in Ngly1-KO embryos. In addition, an abnormal processing of Nrf1 and partial hepatocyte cytoplasmic accumulation of Nrf1 were observed. These results indicated that Ngly1-deletion causes delayed murine liver development, partially caused by the Nrf1 dysfunction, and as a result, causes defects of murine hematopoiesis such as delayed red blood cell maturation (decreased the number of enucleated erythroblast).
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| Academic Significance and Societal Importance of the Research Achievements |
現在まで、造血発生にNgly1による糖鎖脱離・分解が寄与するという報告は世界的にみてもない。本研究では初めて、細胞質での糖鎖脱離・分解に寄与する糖鎖脱離酵素Ngly1が、正常な肝臓および赤血球の発生において重要な役割を果たすことを明らかにした。また、そのメカニズムの一端として転写因子Nrf1が寄与することも明らかにした。造血発生や造血幹細胞については不明な点も残存しているが、本研究でNgly1が関与することが明らかになったので、Ngly1という新しい切り口から残存する不明点の解明に取り組むことで、新たな学術的知見を得られると期待できる。
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