| Project/Area Number |
17390246
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokyo |
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Principal Investigator |
NANGAKU Masaomi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 講師 (90311620)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Toshio Tokai University, School of medicine, Professor, 総合医学研究所, 教授 (10222332)
INAGI Reiko Tokai University, Medicine Res Inst, Associate Professor, 総合医学研究所, 助教授 (50232509)
花房 規男 東京大学, 医学部附属病院, 非常勤医員
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,300,000 (Direct Cost: ¥15,300,000)
Fiscal Year 2006: ¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2005: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | ischemia / hypoxia / chronic kidney failure |
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| Research Abstract |
In order to probe the transcriptomic events and clarify pathophysiological mechanisms of renal injury induced by chronic hypoxia, we employed microarray-based analysis in rat kidneys rendered to chronic hypoxia. Chronic hypoxia of the kidney was induced by unilateral renal artery stenosis with a Goldblatt silver clip. We obtained RNA isolated from the cortex of control kidneys and hypoxic kidneys at 3 and 7 days after induction of renal artery stenosis. Lack of inflammation or other confounding factors at these time points allowed us to clarify a molecular pathogenesis of renal injury induced by chronic hypoxia per se.
Microarray-based analysis identified various categories of genes. Eighty-eight genes were induced over 2.0-fold change the stenotic kidney at 3 days, and 120 genes were up-regulated over 2.0-fold change at 7 days after induction of renal artery stenosis. On the other hand, 26 genes and 48 genes were suppressed under 0.5-fold change at days 3 and 7, respectively. Expression patterns of 96 genes were consistently altered following renal artery stenosis, including 77 genes that were up-regulated over 2-fold and 19 genes down-regulated under 0.5-fold at both periods examined.
We also performed proteomic analysis of kidney with chronic hypoxia and found a paradoxical decrease in expression of Cu/Zn-SOD. Western blot analysis and real-time quantitative PCR analysis confirmed the down-regulation of Cu/Zn SOD in the chronic hypoxic kidney. Further, our laser capture microdissection system showed that the expression of Cu/Zn-SOD was predominant in the tubulointerstitium, and was decreased by chronic hypoxia.
Our studies clarifed a varity of genes whose expression was modified by chronic hypoxia of the kidney, suggesting a framework for understanding drivers of kidney injury in chronic hypoxia and the molecular basis of the pathophysiology in this setting.
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