| Project/Area Number |
11671046
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Saitama Medical School |
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Principal Investigator |
MITARI Tetsuya Saitama Medical School, School of medicine, Pro., 医学部, 教授 (50101374)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUDA Akihiko Saitama Medical School, School of medicine, assistant, 医学部, 助手 (70265411)
KANOUZAWA Kouichi Saitama Medical School, School of medicine, assistant, 医学部, 助手 (10233917)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | podocyte / cytoskeleton / phosphorylated vimentin / CD-68 / IgAN / nephritic syndrome / urinary podocyte / VEGF / vimentin |
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| Research Abstract |
In order to establish the new strategy for the treatment of progressive glomerular diseases, we tried to clarify the cell behaviors of podocyte in various glomerular diseases. Since the cultured glomerular epithelial cells possess the characteristic features of parietal epithelial cell and never produce foot process formation, it seems difficult to identify the cell behaviors of podocyte using culture system. Then, we carried out immunohistological studies using confocal microscopy. Double staining method was employed for identifying podocyte, and anti-podocalyxin antibody was used together with labeled-anti-type VI collagen (alufa-5) antibody, that visualized glomerular basement membrane (GBM). Vimentin, a member of intermediate filaments, is one of the components of cytoskelton of cells, and we previously reported that the vimentin filaments of mitotic cells are phosphorylated by cdc-2 kinase and calcium-calmodulin dependent protein kinase II (CaMK II) in a stage of cell division spe
… More
cific manner. Monoclonal antibodies that specifically reacted with phosphorylation site for cdc-2 kinase or CaMK II were a good tool to analyze cell behavior of podocyte in various glomerular diseases. Phosphorylated vimentin by cdc-2 kinase was detected in the podocyte not only in the early stage of puromycin aminonucleotide treated model, but also in the various human diseases, including IgA glomerulonephritis and focal segmental glomerulosclerosis. Accumulating reports suggest that phenotypic changes of podocyte were recognized in several diseases model. In this study, JAK-3 expression of podocyte was enhanced in IgA nephropathy. CD-68 expression was detected in the podocyte in early phase of crescentic glomerulonephritis. Although it has been thought that podocytes are terminally differentiated and quiescent cells, analysis of podocyte behaviors revealed that changing phenotype and entering to mitotic phase are frequently recognized in verious glomerular diseases
We also analyzed urinary podocalyxin-positive cells that thought to be the podocyte detached from CBM. A part of urinary podocyte was positive for phosphorylated vimentin by cdc-2 kinese. Numbers of urinary podocyte were estimated in groups of patients with IgAN and nephritic syndrome. In the patients with IgAN, the numbers of urinary podocyte correlated with the degree of pioteinuria and hematuria. In the patient with nephritic syndrome, urinary podocyte was disappeared after successful treatment. Serial estimation of the urinary podocyte may be useful marker for prediction of clinical outcome Less
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