| Project/Area Number |
10670154
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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 |
Human pathology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
NAGATA Michio University of Tsukuba, Pathology, Institute of Clinical Medicine, Associate Professor, 臨床医学系, 助教授 (10192238)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Naoki Tokyo Metropolitan Institute of Gerontology, Molecular Pathology, Director, 分子病理室, 室長 (00115940)
WATANABE Teruo University of Tsukuba, Pathology, Institute of Basic Medical sciences, Professor, 基礎医学系, 教授 (40037396)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | podocyte / parietal epithelial cells / glomerulosclerosis / cell cycle / cell cycle inhibitor / nephron / IL-4 / IL-4 / ボーマン嚢上皮細胞 / cyclin kinase inhibitor / 体硬化 / 器官培養 / GFP / Podocyte / differentiation / Cell cycle / phenotype |
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| Research Abstract |
This project was aimed to find the mechanism involving cell cycle reguration of glomerlular epithelial cells (podocytes). During first year of 1998, we found that cell cycle quiescent and podocyte differentiation was closely correlated in human fetal kidneys. Cell cycle stunt is tightly cassociated with up-regulation of cell cycle inhibitors, p27 and p57. Cell cycle promotion of presumptive podocytes was partly determined by cyclin A, B1 and D1. In addition, we found low expression of CKIs in cellular crescents and cellular lesion in focal glomeruloscleorsis in human biopsy materials. These proliferating cells virtually expressed cytokeratin indicating parietal epithelial cell phenotype. Thus PECs compensate podocyte loss is an actual pathology promoting glomerulosclerosis.
The second year of 1999, we performed in vitro study. Metanephric organ culture showed up-reguration of p27, but not p57 in concert with podocyte differentiation. Thus p27 plays predominant role for the podocyte differentiation and cell cycle stunt. Next, we looked at the effect of Interleukin-4 in podocyte cell culture. We found IL4 stimulate podocyte cell line to form Dome shape. Thus IL-4 may modify cell attachment system, i.e., focal contact.. Finally we used green fluorescent transgenic mice to determine whether inserted promoter is activated with differentiation. Fetal kidneys and metanephric culture system demonstrated podocyte glowing in capillary loop stage. The stimulant for this hybrid promoter needs further investigation.
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