| Project/Area Number |
13671112
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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 | Mie University |
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Principal Investigator |
NOMURA Shinsuke Mie University, School of Medicine, Associate Professor, 医学部附属病院, 助教授 (20198625)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Ichiro Shigei Medical Institute, Department of Ultrastructured Pathology, Chief Director, 超微病理部門, 部長(研究職)
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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: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Alport's syndrome / type IV collagen / glomerular basement membrane / Cyclosporine A / 遺伝子性糸球体腎炎 / IV型コラーゲンα / 遺伝性糸球体腎炎 / 進行性腎障害 |
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| Research Abstract |
1)Early GBM lesion in Alport-mice
Observation of lesions in developping glomeruli using COL4A3-/-mouse as a human Alport's syndrome (AS) model has revealed that the most characteristic change in such period is the GBM outpockets observed through an electron microscope. Even during the period before the lamellation and splitting in the GBM is evident, the outpockets were observed in the mice more frequently and widely than those from wild type mice. It had been thought that outpockets are formed in the process of expansion of the basement membranes of developing glomeruli. However, the relationship between formation of outpockets and the changes such as lamellation and splitting appearing subsequently in the course of development should be studied.
2) Therapeutic approach for inhibiting the progression of Alport syndrome
Although several researchers have reported on human subjects who responded favorably to cyclosporine A (CyA), the reason why this immunosuppressant is effective in AS remains unclear. We administered CyA (3 mg/kg) to COL4A3-/-mice for only two weeks subcutaneouslly to evaluate its therapeutic effect and study the action mechanism. In the early treatment group in which CyA was started from 2 weeks of age. glomerulosclerosis and interstitial fibrosis at 8 weeks of age were remarkably inhibited. Immunohistologically. TGF-beta expression in glomerular mesangium was inhibited. In the late treatment group in which started 4weeks of age, the results were. These findings support the empirical, reports that CyA is effective for treatment of human AS. Although CyA is a costful and can bring significant adverse reactions, it should be considered as one of the therapeutic drugs.
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