| Project/Area Number |
09671186
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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 | KAWASAKI UNIVERSITY OF MEDICAL WELFARE (1998)
Kawasaki Medical School (1997) |
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Principal Investigator |
OSAWA Gengo Kawasaki University of Medical Wefare Faculty of Medical Welfare, Professor, 医療福祉学部, 教授 (00018368)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Tamaki Kawasaki Medical School, Department of Medicine, Assisatant Professor, 医学部, 講師 (30187124)
除 義之 川崎医科大学, 医学部, 助手 (90235812)
北野 裕一 川崎医科大学, 医学部, 講師 (60177855)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Podocyte / TGF-B / Cyclin-CDK / cyclin kinase inhibitor (CKI) family / p21 / p27 / Osteopontin / Tenascin / BMP7 / 糸球体荒廃像 / Bowman嚢上皮細胞 / 尿細管間質病変 |
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| Research Abstract |
Podocytes are mostly present in the late G1 phase of the cell cycle even in the proliferative state, and there is no increase in the number of cells. As for the cyclin kinase inhibitor (CKI) family, which suppresses shifting of the cell cycle from the G i to the S phase, p21 and p27 have been identified. Regarding the number of p27-positive cells in podocytes, changes due to administration of FGF2 were not observed, but an increase in p21-positive podocytes was noted. These findings suggest that the reason most podocytes remain in the late GL phase might be upregulation of p21. Furthermore, FGF2 induced podocyte injury related to the transit cell cycle. When two sets of PAN rats were compared, the number of BrdU-positive cells was clearly greater in the rats administered FGF2. This finding demonstrated that a few podocytes entered the DNA synthesis phase. The number of bi - or multi- nucleated podocytes was counted in these rats. Our hypothesis is that podocytes entering the S phase are associated with FGF2-idced cell damage. We have shown that TGF-B isoforms and receptors increase with the podocytes of various glomerular injury models. The smad family was recently isolated and identified in the signalling of TGF-B.Expression of the smad family was observed in the podocytes of various glomerular injury models. TGF-B increases the expression of p21 in certain cells in vitro. Taken together, increases in p21 expression in podocytes may be due to the upregulation of TGF-B.We propose that p21 protects podocytes against damage by preventing damaged cells from entering the cell cycle.
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