| Project/Area Number |
02671029
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | TOKYO METROPOLITAN INSTITUTE OF GERONTOLOGY |
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Principal Investigator |
KAJI Kazuhiko TOKYO Met.Inst.geront. Senior Res., 老化科学技術研究系・アイソトープ部門, 主査研究員 (40073019)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | growth factor / growth inhibitor / apoptosis / fibroblast / endothelial cell / PDGF / TGFbeta / FGF / 増殖阻害 / TGFβ / レセプター / 心筋梗塞 / 血管内皮細胞 / 無血清培養法 / TGFβレセプタ- / TGFβ1 / 抗体 |
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| Research Abstract |
1 PDGF, FGF as well as EGF support the cell growth of human diploid fibroblast including WI-38 cells in serum-free MCDB-104 medium supplemented with insulin, transferrin and dexamethasone. The optimal concentrations of these hormones and growth factors change little throughout the lifespan of these cells, although the magnitude of the response declines progressively. Transforming growth factor-beta (TGF-beta) inhibits the proliferation of these fibroblasts in serum-free media supplemented with EGF or PDGF. TGF-beta also induces some morphological changed in these cells. After removal of TGF-beta, the cell revert from the above effects.
2 Survival and proliferation of many types of vascular endothelial cells are influenced by fibroblast growth factor (FGF). Removal of FGF from the medium of human umbilical vein endothelial cells (HUVEC) in culture resulted in death of the cells. The death caused by deprivation of FGF is active death or apoptosis, and the process of apoptosis can be inhibited by cycloheximide. The process of active death of vascular endothelial cells is inhibited by FGF. This mechanism may be important for the regulation of vascular organization through the degeneration of vessels.
3 Coronary collateral vessels reduced damage to ischemic myocardium after coronary obstruction. Factors that stimulate collateral formation are expected to have ameliorating effects on myocardial infarction. In a canine experimental myocardial infarct model, intracornary injection of bFGF improved, cardiac systolic function and reduced infarct size. Treatment with bFGF increased the number of arterioles and capillaries in the infarct. The application of bFGF might bring about a therapeutic modality for the salvage of infarcted myocardium.
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