| Project/Area Number |
62870094
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MUROTA Sei-itsu Tokyo Medical and Dental University, Faculty of Dentistry, Professor, 歯学部, 教授 (50072989)
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| Co-Investigator(Kenkyū-buntansha) |
MORITA Ikuo Tokyo Medical and Dental University, Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (60100129)
YAMAMOTO Akihiro Terumo Corp., Technical Research and Development Division, Head, 医薬品開発部, 部長
WAKABAYASHI Toshio Terumo Corp., Technical Research and Development Division, Head, 技術開発部, 部長
IINO Yasuhiko Tokyo Medical and Dental University, Faculty of Medicine, Lecturer, 医学部, 講師 (60134706)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 1989: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1988: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1987: ¥6,500,000 (Direct Cost: ¥6,500,000)
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| Keywords | arachidonic acid metabolism / cultured mesangial cell / angiotensin II / endothelin / immune complex nephritis / puromycin aminonucleoside nephrosis / mesangial cell proliferative nephritis / 腎炎 / 糸球体 / アラキドン酸 / リポキシゲナ-ゼ / HETE / リポキシゲナーゼ / 12ーリポキシゲナーゼ |
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| Research Abstract |
The project was carried out in order to clarify the involvement of arachidonic acid metabolites, particularly lipoxygenase products, in glomerulonephritis(GN). The effect of some lipoxygenase inhibitors(TMK-688, TER-61021, BW-A4C) on four types of experimental GN model induced in rats were investigated and following results were obtained. 1)In the immune complex GN (bovine serum albumin GN), successive administration of the lipoxygenase inhibitor TMK-688 caused decrease in the proteinuria. 2)The proteinuria in non-immunologically induced nephrosis(puromycin aminonucleoside nephrosis) was not inhibited by the lipoxygenase inhibitor TER-61021.3)In another GN model induced by immune complex of cationic bovine gamma globulin, no significant reduction of proteinuria was observed by the treatment of the lipoxygenase inhibitor TER-61021.4)Mesangioproliferative GN was induced by a single intravenous injection of anti-rat Thy 1.1 monoclonal antibody. The lipoxygenase inhibitor BW-A4C caused dec
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rease in the expansion of mesangial area and the proteinuria. These results obtained in vivo indicate that the lipoxygenase products may play some roles in pathogenesis in the chronic GN and the mesangioproliferative GN. Therefore, next we investigated the effects of lipoxygenase and cyclooxygenase inhibitors on cultured mesangial cell growth in vitro. The lipoxygenase inhibitors inhibited the mesangial cell growth stimulated by 20% FCS. On the other hand, the cyclooxygenase inhibitor enhanced the growth of mesangial cells under the same condition. These results indicate that the growth of mesangial cells may be regulated by some arachidonic acid metabolites. Angiotensin II or endothelin also stimulated the growth of mesangial cells in the presence of insulin. The growth of mesangial cells stimulated by angiotensin II was inhibited by the lipoxygenase inhibitors. The effect of the lipoxygenase inhibitors on mesangial cell growth stimulated by endothelin is now under investigation. These results obtained both in vivo and in vitro suggest that the lipoxygenase inhibitors may be beneficial for the patients with mesangloproliferative GN and chronic GN. Less
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