| Project/Area Number |
19K17722
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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 53040:Nephrology-related
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Yokote Shinya 東京慈恵会医科大学, 医学部, 助教 (30459656)
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| Project Period (FY) |
2019-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 腎臓再生 / 後腎移植 / 後腎 |
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| Outline of Research at the Start |
申請者は、再生腎臓の尿排泄路システムであるStepwise Peristaltic Ureter system : SWPU systemを開発した。今回の研究では、SWPU systemを用いて再生した新規腎臓をさらに大型化し尿量を増加させる方法を開発し、臨床応用に向けての研究基盤を確立することが目標である。
新規腎臓を大型化するために①VEGF等の液性因子や間葉系幹細胞の新規腎臓の発育への影響を精査し、②利尿剤であるTolvaptanが新規腎臓の尿量増加に寄与するかを検討する。また、③無腎ラットの長期予後を改善しうるかについても検討することを目的とする。
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| Outline of Final Research Achievements |
1) Analysis of the effect of HIF-PH inhibitor administration on the development of regenerated kidneys.
Metanephroi with a bladder (cloaca) was transplanted into LEWIS rats. Rats were divided into two groups. The HIF-PH group received Roxadustat and the control group received a sham drug. SWPU was performed 4 weeks after transplantation. 8 weeks after transplantationnew kidney weights and renal histology were evaluated. Although new kidney weight was increased in the HIF-PH group compared to the control group, there was no obvious significant difference in new kidney weight between the two groups. 2) Effect of Tolvaptan on regenerating kidneys. LEWIS cloaca is transplanted into rats. Rats were divided into 2 groups. The tolvaptan group received oral administration of tolvaptan, while the control group received received a sham drug orally. At 4 weeks after transplantation, SWPU was performed. tolvaptan group showed a trend toward increased urinary cloaca volume.
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| Academic Significance and Societal Importance of the Research Achievements |
SWPUを用いた再生腎臓の大型化、尿量の増加を可能にする薬剤についての検討を行った。ある種の薬剤には再生腎臓の大型化や尿量の増加が期待できるという本研究の結果は、SWPUを用いた腎臓再生が臨床応用するために重要な所見であったと思われる。今後、研究を継続し、これらの知見を用いて実際にSWPUを用いた腎臓再生により腎不全動物の予後を改善することができれば、さらにSWPUを用いた腎臓再生の臨床応用に近づくと思われる。
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