| Project/Area Number |
17K09679
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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 |
Kidney internal medicine
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| Research Institution | Hokkaido University |
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Principal Investigator |
Saori Nishio 北海道大学, 大学病院, 講師 (90463736)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 多発性嚢胞腎 / バイオマーカー / アミノ酸 / LAT1 / 遺伝子解析 / mTOR経路 / MAPK経路 / 予後予測 / 常染色体優性多発性嚢胞腎 / 予後 / 必須アミノ酸 |
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| Outline of Final Research Achievements |
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. In this study, I aimed to assess the predictive value of genotypic and clinical factors and to develop a prognostic algorithm to forecast the progression to ESRD in patients with ADPKD. I completed collection the clinical data and analysis of genotype. I will publish them in the near future.
In addition, I analyzed the mechanism of cyst progression by administering BCAA dissolved in the drinking water to Pkd1model mice. I found Branched-chain amino acids (BCAA) accelerated both kidney and liver cysts progression by mTOR and MAPK/ERK pathways . Furthermore, I found that L-type amino acid transporter 1 (LAT-1), which is amino acid transporter, was upregulated in cyst-lining cells. These results have been published in Kidney International.
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| Academic Significance and Societal Importance of the Research Achievements |
ADPKDはすべての患者が末期腎不全に至るわけではなく、同じ家系でも進行に差がある。予後予測因子を明らかにすることは、治療すべき患者を明確にするために非常に重要である。今回の研究で予後予測因子が明らかにできれば、今後の治療に非常に役立つ事ができる。また、ADPKDモデルマウスに必須アミノ酸負荷することで、嚢胞が悪化することが明らかになったことで、ADPKD患者が必須アミノ酸を取り過ぎない方がよい可能性が示唆された。更に嚢胞上皮細胞にLAT1の発現が認められた。今後はLAT1をターゲットとした、治療法の開発を行っていこうと考えており、新規治療に結びつく可能性がある。
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