| Project/Area Number |
11671060
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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 | Kanazawa Medical University |
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Principal Investigator |
TOMOSUGI Naohisa Kanazawa Medical University, Division of Nephrology, Asociate Professor, 医学部, 助教授 (80155580)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | recombinant adenovirus / gene transfer / macrophage migration inhibitory factor (MIF) / glomerulonephritis / ischemic reperfusion / acid stress / renal transplantation / renal interstitial injury / アデノウイルス / MIF |
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| Research Abstract |
In the progress of glomerulonephritis, macrophages infiltrated in the glomeruli play an important role. Macrophage migration inhibitory factor (MIF) inhibites random migration of macrophages and mediates macrophage accumulation and activation. In 1999 fiscal year study, MIF was forced to release in the blood from muscle transfected with recombinant adenovirus since the initial stage of glomerulonephritis. The result showed that the progress of the glomerulonephritis was suppressed by gene transfer of MIF.It is indicated that the recruit of macrophage from the blood streem to glomeruli was controled by MIF.
Physiologically, MIF is expressed in brain and kidney at high levels. Espetially renal tubular cells contained high baseline levels of intracellular MIF, and it is supposed that intracellular MIF is released upon oxidative stress and/or immune stimulation. In 2000 fiscal year study, renal reaction for such oxidative stress was examined from the point of the release of MIF.Intracellular MIF of culture mesangium cells was released in medium under oxidative stress by H2O2. It is different from the mechanisms of reaction against TNF which induces de novo MIF protein synthesis through transscription and translation. After renal oxidative stress induced by ischemia-reperfusion of the rat renal artery, intracellular MIF of the tubular cells reduced obviously and the levels of serum MIF elevated, which may be based on the release of storage MIF in the tubular cells by the ischemia stimulation. Clinically, in patients with renal graft rejection and IgA nephropathy which were sometime accompanied by the damages of renal tubular interstitial tissue, the serum MIF value was parallel to the activity of these lesions. These results indicate that the detection of serum MIF is expected as useful evaluation tool of therapy, although the physiological significance of released MIF is still unknown.
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