| Project/Area Number |
13671106
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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 | Hamamatsu University School of Medicine |
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Principal Investigator |
HISHIDA Akira Hamamatsu University, School of Medicine, First Department of Medicine, Professor, 医学部, 教授 (70111812)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Akihiko Hamamatsu University, School of Medicine, First Department of Medicine, Instructor, 医学部附属病院, 助手 (60324357)
FUJIGAKI Yoshihide Hamamatsu University, School of Medicine, First Department of Medicine, Instructor, 医学部, 助手 (20283351)
YONEMURA Katsuhiko Hamamatsu University, School of Medicine, Hemodialysis Unit Associate Professor, 医学部附属病院, 助教授 (40252176)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | csplatin / acute renal failure / p21 / p27 / cyclin D1 / DNA repair / sodium arsenite / IGF-1 / IGF-1 / p53 / 細胞周期調節 / アポトーシス / 急性腎不全に対する抵抗性獲得 |
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| Research Abstract |
In CDDP-induced acute renal failure(ARF), the damaged tubular cells undergo DNA repair or apoptotic cell death. We hypothesized that damaged tubular cells would stop the cell cycle at G1 and accelerate DNA repair. In this study, we evaluated whether the cyclins and cyclin dependent kinase inhibitors, which are cell cycle regulation factors, are increased in CDDP-induced ARF kidneys. We also studied the expression of DNA repair markers and evaluated whether the expression of se markers of cell cycle regulations and DNA repair are related to the severity of ARF. In CDDP-induced ARF, the overexpressions of p21, p27, cyclin D_1 and PCNA were observed on day 3. The increase in PCNA was not associated with the increase in BrdU incorporation, suggesting that the increase in PCNA positive cells might reflect the increased DNA repair rather than the increased cell proliferation. The pretreatment with CDDP 14 days prior to the second CDDP injection attenuated the decline of kidney function and tubular damage in CDDP-induced ARF. This attenuation was associated with the increases in p21 and PCNA. The preadministration of sodium arsenite augmented the expression of p27 and PCNA and suppressed the expression of cyclin D_1, which were followed by the functional and morphological attenuation of the degree of ARF. The administration of IGF-1 also increased the expression of p21 and PCNA and attenuated the increase in cyclin D_1 and the decline of renal function. In summary, the increases in p21, p27 and PCNA and the decrease in cyclin D_1 were associated with the attenuation of CDDP-induced ARF, suggesting an important role of cell cycle regulation and DNA repair in the development of CDDP-induced ARF.
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