| Project/Area Number |
62570276
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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 |
Legal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
MORISAKI Nobuhiro The Second Department of Internal Medicine, 医学部第二内科, 助手 (40174411)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRAI Kohji The Second Department of Internal Medicine, 医学部第二内科, 助手 (00150269)
SAITO Yasushi The Second Department of Internal Medicine, 医学部第二内科, 講師 (50101358)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | smooth muscle cells / atherosclerosis / growth factor / autocrine / smooth muscle cell derived growth factor (SDGF) / platelet derived growth factor (PDGF) / 内皮細胞 / 平滑筋細胞由来増殖因子 / 家兎 |
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| Research Abstract |
Results: 1. Cultured intimal aortic smooth muscle cells (I-SMC) grew faster than medial SMC. 2. M-SMC secreted a mitogen after 4th passages whereas I-SMC did at earlier passages. This factor was named SDGF. 3. Co-culture of M-SMC with endothelial cells induced M-SMC to grow faster together with increased SDGF secre-tion. 4. SDGF worked on rabbit and rat SMC and human fibroblasts but not on endothelial cells. 5.Physicochemical properties of SDGF were: (1) non dialysable (2) sensitive to trypsin (3) labile at heating (100゜C, 10') and reduction (4) stable at acidic condition (5) Molecular weight, 8700(Sephadex G-75) (6) PI was 5.9 and 4.2.6. Combination with known growth factors: (1) The activity was not inhibited by anti-PDGF antibody. SDGF did not share PDGF receptors. (2) Somatomedin C was not detected in conditioned medium. (3) showed synergistical effects both with com-petence factors (PDGF, FGF) and progression factors(Somatomedin C, EGF). Even worked in the presence of optimal doses of PDGF and EGF. Did not show the property of competence factors. 7. Purification: (1) adsorbed to DEAE Sephadex A-25 and eluted with IM NaCl. (2) showed 5.9 and 4.2 of PI value in isoelectric focusing. (3) eluted to the portion of molecular weight 8700 in Sephadex G-75 gelfiltration. Conclusions: It was suggested that (1) In vivo M-SMC migrate to the intima, acquire the ability to secrete SDGF by the modulation with endothelial cells (autocrine system), and then proliferate by themselves to form the intimal thickening. (2) SDGF is a new polypeptide growth factor which stimulates a different pathway for DNA synthesis from that stimulated by PDGF.
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