| Project/Area Number |
13557085
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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 | 展開研究 |
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| Research Field |
Kidney internal medicine
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
MATSUO Seiichi Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (70190410)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Hirokazu Aichi Medical College School of Medicine, Assistant Professor, 医学部, 講師 (30301625)
MORITA Yoshiki Nagoya University Hospital, Medical Staff, 医学部附属病院, 助手 (10335044)
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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 |
¥8,900,000 (Direct Cost: ¥8,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | complement / anaphylatoxin / C5a / gene transfer / carboxypeptidase R (CPR) / rat / glomerulonephritis / anti-GBM antibody / 腎障害 / 血栓形成性糸球体腎炎 / トロンボモジュリン |
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| Research Abstract |
In the present study, we investigated the possibility that arginine specific carboxypeptidase (CPR) is used as the effective anti-naphylatoxin agent in vivo. It is well known that CPR inactivate anaphylatoxins such as C5a by removing the argine residue. In order to test this hypothesis, we first cloned the rat homolog of human pro-carboxypeptidase R (pro-CPR). We then evaluated the efficacy and the reliability of in vivo gene transfer technique by retrograde injection of human erythropoietin (EPO) gene via tail vein. The EPO gene was efficiently introduced into the liver cells by this method. Then, we used rat homolog of pro-CPR gene in order to increase the concentration of pro-CPR in plasma. We found that 2 to 4 folds increase of plasma pro-CPR concentration was achieved. Then we induced anaphylatoxin-dependent diseases in rats. Rats treated with small amount of LPS and anti-glomerular basement membrane antibody (anti-GBM) showed very severe glomerular lesions characterized by the thrombotic glomerular capillary inflammation. Rats died within 24 hours after induction of diseases when they are not treated with anti-C5a receptor antagonists or thrombomodulin. The effects of pro-CPR gene transfer to these rats were limited. These results suggest that the further study is needed, for example, by the gene transfer of active form of CPR.
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