Inhibition of the binding of basic fibroblast growth factor to its receptor and angiogenesis by synthetic peptides related to platelet factor 4

血小板因子 4 相关合成肽抑制碱性成纤维细胞生长因子与其受体的结合和血管生成

• 批准号: 03670629
• 负责人: SATO Yasufumi
• 金额: $ 1.34万
• 依托单位: KYUSHU UNIVERSITY OITA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670629/
• 关键词: platelet factor 4(PF-4); basic fibroblast growth factor(BFGF); angiogenesis; heparin binding; synthetic peptide; FK506; Liver Regeneration; Hepatectomy; Protein Content; DNA Content; DNA Synthesis; Liver Enzyme

We have found that platelet factor 4 (PF-4) blocks the binding of basic fibroblast growth factor (bFGF) to its receptor and inhibits the spontaneous tube formation of endothelial cells in type 1 collagen gel (in vitro angiogenesis). These biological activities localize at the carboxyl-terminal heparin binding domain of the PF-4 molecule. A synthetic peptide composed with at least 10 amino acids (KKIIKKLLES : C-10) of carboxyl terminal PF-4 retains these activities. It is speculated that the cluster of basic amino acids, lysine, plays an important role, In order to obtain an active synthetic peptide with minimal amino acids, we composed KKIIKK (C-6) and compared its activities with that of C-10. We could not observe any biological activities in C-6. Therefore, not only electric charges but also three-dimensional structure of the peptide might be important to express its activity. Finally, we tested the in vivo effect of C-10 whether or not it blocked angiogenesis after the inoculation of tumor cells in mice. C-10 had no significant effect on angiogenesis induced by tumor cells. These results indicates that multiple factors may be involved in tumor angiogenesis, and the elimination of the effect of bFGF may not be sufficient.

我们发现，血小板第4因子(PF-4)阻断了碱性成纤维细胞生长因子(BFGF)与其受体的结合，并抑制了I型胶原凝胶中内皮细胞的自发管形成(体外血管生成)。这些生物活性定位于PF-4分子的羧基末端肝素结合区。由至少10个氨基酸组成的合成肽(KKIIKKLLES：C-10)的羧基末端PF-4保持这些活性。我们合成了KKIIKK(C-6)，并将其与C-10的活性进行了比较。我们在C-6中没有观察到任何生物活性。因此，不仅是电荷，而且多肽的三维结构可能是表达其活性的重要因素。最后，我们测试了C-10对小鼠肿瘤细胞接种后是否阻断血管生成的体内作用。C-10对肿瘤细胞诱导的血管生成无明显影响。这些结果表明，肿瘤血管生成可能涉及多个因素，仅消除bFGF的作用可能是不够的。