| Project/Area Number |
01480163
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Niigata University |
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Principal Investigator |
SHIMIZU Fujio Niigata University School of Medicine, Professor, 医学部, 教授 (40012728)
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| Co-Investigator(Kenkyū-buntansha) |
MORIOKA Tetsuo Niigata University School of Medicine, Assistant, 医学部, 助手 (00210146)
OITE Takashi Niigata University School of Medicine, Associate professor, 医学部, 助教授 (60018744)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥6,000,000 (Direct Cost: ¥6,000,000)
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| Keywords | Monoclonal Antibody / Proteinuria / Glomerular Epithelial Cell / Mesangium / Mesangiolysis / Cultured Cell / 腎糸球体硬化 / 補体 / slit diaphragm / 腎糸球体上皮細胞 / アミノヌクレオシド腎症 |
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| Research Abstract |
The purpose of this study is to analyze the mechanism of renal injury at the molecular level by application of monoclonal antibody (MA). We have produced 2 kinds of MAs which induce a massive proteinuria in rats by a single intravenous injection. MA 5-1-6, IgG1, binds to the surface of glomerular epithelial foot processes, mainly to slit diaphragm MA 1-22-3, IgG3, binds to the limited surface of mesangial cells facing endothelial cells. The minimum dose of both MAs required to induce proteinuria is very small in comparison with already reported one in several kinds of experimental glomerulonephritides. This also indicates that each epitope recognized by both MAs is a very limited point which plays the critical role in keeping the normal glomerular permeability.
The study of our MAs indicates that a chain reaction leading to proteinuria with or without mesangial lesions is initiated by the reaction between 2 defined molecules (MA and very specific surface molecules of glomerular cells). In the case of MA 5-1-6 the proteinuria is induced without the involvement of the classical mediators of immune injury such as complement or leukocytes.
We have demonstrated that glomerular cell injury depends on an epitope specific interaction between a cell surface epitope as a receptor and a MA as a ligand. This seems to be an entirely new mechanism by which proteinuria can be induced. The simplicity of MA-induced in vivo models is ideal for analyzing the immunopathology of induced lesions at molecular levels.
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