Effect of V-ATPase inhibition in renal fibrosis
Project/Area Number |
17K16092
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
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Research Institution | Tohoku Medical and Pharmaceutical University |
Principal Investigator |
Yabana Ikuko 東北医科薬科大学, 医学部, 助教 (60778596)
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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Keywords | 腎臓 / 線維化 / 細胞内タンパク質輸送 / 酸性オルガネラ / V-ATPase / 細胞内蛋白輸送 / 腎線維化 / 慢性腎臓病 |
Outline of Final Research Achievements |
The vacuolar ATPase (V-ATPase) regulates the pH of organelle vesicles and is involved in the intracellular and extracellular transport of proteins. We investigated the effect of V-ATPase inhibition on fibrosis in the kidney. First, we examined the effect of bafilomycin (BAF: V-ATPase inhibitor) on TGF-β-induced fibrosis in M1 cells derived from mouse renal cortical collecting ducts. The fibrotic proteins induced by TGF-β were trapped in the cytoplasmic organelle by V-ATPase inhibition. Next, we investigated the effect of BAF on renal fibrosis in a renal fibrosis model, UUO. Fibrosis induced by the UUO was partially inhibited in the BAF-treated group compared to the control group. However, the increase in liver weight and hepatic fibrosis were observed, meaning the hepatotoxicity was stronger than the inhibitory effect of BAF on fibrosis.
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Academic Significance and Societal Importance of the Research Achievements |
腎線維化の進展にはV-ATPaseにより調節される細胞内酸性オルガネラを介したタンパク質輸送が関与している。障害により誘導された線維化タンパク質は、V-ATPase阻害により細胞外への輸送が抑制され、細胞内の酸性オルガネラにとどまるようになる。組織障害に伴う線維化に対し、障害を受けた組織特異的なV-ATPase阻害により線維化を抑制し、組織を保護できる可能性が示唆された。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells.2018
Author(s)
1: Oba-Yabana I, Mori T, Takahashi C, Hirose T, Ohsaki Y, Kinugasa S, Muroya Y, Sato E, Nguyen G, Piedagnel R, Ronco PM, Totsune K, Ito S
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 2648-2648
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Exon 4-encoded domain of (pro)renin receptor impairs several V-ATPase-mediated functions.2019
Author(s)
Hirose T, Cabrera-Socorro A, Matsuki T, Takahashi C, Oba-Yabana I, Kinugasa S, Muroya Y, Tani J, Nguyen G, Groszer M, Ito S, Mori T.
Organizer
ISARSH2019
Related Report
Int'l Joint Research
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[Presentation] 光学顕微鏡用腎組織標本の低真空走査電子顕微鏡を用いた観察.2019
Author(s)
廣瀬卓男, 髙橋知香, 松木琢磨, 中山晋吾, 衣笠哲史, 矢花郁子, 加藤季子, 関敬之, 中村はな, 谷淳一, 森建文.
Organizer
第48回宮城県腎不全研究会
Related Report
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