| Project/Area Number |
17K09684
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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 | University of Tsukuba |
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Principal Investigator |
USUI JOICHI 筑波大学, 医学医療系, 准教授 (70447340)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 内科 / 発生 / 老化 / 病理学 / 腎臓内科学 |
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| Outline of Final Research Achievements |
Based on biological research about organ development and aging, 2 projects were progressed, A: TCF21 expression in various kidney diseases, B: Renal involvements of mitochondrial DNA deletion-dependent model. A: In vivo TCF21 experiments, we investigated TCF21 expression in vivo. The association between histological TCF21 expression and UP/urinary TCF21 was statistically significant. In vitro experiments using Tcf21-expressing podocyte cell line, we could observe Tcf21-dependent effects, related with actin cytoskeleton dysregulation and apoptosis. Therefore, TCF21 expression changes functional significance in injured podocytes. B: We focused on the glomerular injury of mito-miceΔ and investigated the pathogenesis of their renal involvement. The proteinuria developed dependent with higher mitochondrial DNA deletion, more than 90% deletion. Mito-miceΔ with proteinuria histologically revealed FSGS. The podocytes are the main target of mitochondrial dysfunction in the kidney.
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| Academic Significance and Societal Importance of the Research Achievements |
発生や老化と疾患発症のメカニズムの共通項は多く、腎臓病発症でも同様であることを証明した。TCF21発現は糸球体硬化への共通機構であるポドサイト障害と関連性があり、予後指標である蛋白尿との相関も確認した。そのため、臨床応用状、糸球体疾患の鑑別、治療反応性のバイオマーカーの候補となる。さらに治療ターゲットとして蛋白尿制御の起点となる可能性があり、新規治療法の開発に繋がりうる。
ミトコンドリア変異蓄積型のポドサイト障害にその変異率、加齢が影響しており、加齢性糸球体硬化のメカニズムを明らかにできる疾患モデルとして活用可能である。近年増加傾向の高齢者腎障害メカニズム解明を介し、その診療向上に寄与しうる。
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