Analysis of a factor and mechanism of cyst progression
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 |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Hokkaido University |
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 |
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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Report
(4 results)
Research Products
(12 results)
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[Journal Article] The relationship between liver cyst volume and QOL in Japanese ADPKD patients.2020
Author(s)
Muto S, Ando M, Nishio S, Hanaoka K, Ubara Y, Narita I, Kamura K, Mochizuki T, Tsuchiya K, Tsuruya K, Horie S
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Journal Title
Clin Exp Nephrol.
Volume: 24
Issue: 4
Pages: 314-322
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease2019
Author(s)
Tsukiyama T, Kobayashi K, Nakaya M, Iwatani C, Seita Y, Tsuchiya H, Matsushita J, Kitajima K, Kawamoto I, Nakagawa T, Fukuda K, Iwakiri T, Izumi H, Itagaki I, Kume S, Maegawa H, Nishinakamura R, Nishio, Nakamura S, Kawauchi A, Ema M
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Journal Title
Nature Communications
Volume: 10 (1)
Issue: 1
Pages: 5517-5517
DOI
NAID
Related Report
Peer Reviewed / Open Access
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