Studies on mitochondrial function of podocyte, and its role for proteinuria and glomerular sclerosis.
Project/Area Number |
18590879
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | University of Tsukuba |
Principal Investigator |
YAMAGATA Kunihiro University of Tsukuba, Department of Nephrology, Graduate School of Comprehensive Human Sciences, professor (90312850)
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Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yoshio Juntendo University, School of Medicine, Visiting Assistant Professor (50359577)
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Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | Mitochondria / Mitocondirial DNA / slit-membrane proteins / glomerular epithelial cells / mitochondurial DNA depletion / ミトコンドリアDNA / マウスモデル / ネフリン / ポドシン |
Research Abstract |
In a mito-mouse, which has 4698bp deletion mutation of mitochondrial (mt) DNA, dies from renal failure complicating with focal glomerular sclerosis (FGS) lesion, responding to increasing amount of mutation rate of mtDNA. We try to analyze mechanisms for developing FGS lesion in mito-mouse in this study. In mito-mouse, proteinuria was detected in a mouse with the mutatied mtDNA exceeding 70% at the age of 18 weeks, which came to the peak at the age of 20weeks, then finally died at the age of 22weeks. Proteinuria was also detected in a mouse with the mutation rate between 50-69% at the age of 20weeks, although it could live until 28weeks while proteinuria gradually had increased. In the case of a mouse with the mutation rate between 10-49%, proteinuria was slightly observed at the age of 28weeks. A mouse with the mutation rate exceeding 70% revealed FGS lesions after the age of 20weeks, which developed global sclerosis at high rate afterwards. The expression levels of both intraglomerular nephrin and podocin increased when proteinuria level came to the peak point. The mRNA of both proteins was observed after the peak of proteinuria, nevertheless, the production of proteins, as well as that of mRNA, both dropped down afterwards. From our study, accumulation of abnormal mtDNA in glomerular epithelium results in up-regulation of slit membrane protein and mRNA during nephritic phase, however, with ageing and more accumulated abnormal mtDNA results in detachment of glomerular epithelium from GBM and forms FGS lesion.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] A novel apolipoprotein E mutation, ApoE Tsukuba(Arg 114 Cys), in lipoproteinglomerulopathy2008
Author(s)
Hagiwara M, Yamagata K, Matsunaga T, Arakawa Y, Usui J, Shimizu Y, Aita K, Nagata M, Koyama Y, Zhang B, Mastunaga A, Saku K, Saito T
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Journal Title
Nephronl Dial Transplant 23. 1
Pages: 381-384
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoproteinglomerulopathy.2008
Author(s)
Hagiwara M, Yamagata K, Matsunaga T, Arakawa Y, Usui J, Shimizu Y, Aita K, Nagata M, Koyama A, Zhang B, Mastunaga A, Saku K, Saito T.
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Journal Title
Nephronl Dial Transplant 23・1
Pages: 381-384
Related Report
Peer Reviewed
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[Journal Article] Blood flow analysis of the head and lower limbs by the laser Doppler bloodflowmeter during LDL apheresis.2007
Author(s)
Ebiharal, Sato T, Hirayama K, Seki M, Enami T, Kawahara H, Niwayama J, Miyahara T, Sbibata M, Maeda N, Kurosawa T, Yamagata K, Sanaka T.
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Journal Title
Ther Apher Dial 11・5
Pages: 325-330
Related Report
Peer Reviewed
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[Journal Article] A novel apolipoprotein E mutation, ApoE Tsukuba(Arg 114 Cys), in lipoproteinglomerulopathy.2003
Author(s)
Hagiwara M, Yamagata K, Matsunaga T, Arakawa Y, Usui J, S himizu Y, Aita K, Nagata M, Koyama A, Zhang B, Mastunaga A, Saku K, Saito T.
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Journal Title
Nephronl Dial Transplant
Pages: 2008-2008
Description
「研究成果報告書概要(和文)」より
Related Report