Abramovitch R, Neeman M, Reich R, Stein I, Keshet E, Abraham J, Solomon A, Marikovsky M
Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
FEBS Lett. 1998 Apr 3;425(3):441-7. doi: 10.1016/s0014-5793(98)00283-x.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen and migration factor for vascular smooth muscle cells (SMC), promoted neovascularization in vivo in the rabbit cornea. MRI demonstrated quantitatively the angiogenic effect of HB-EGF when introduced subcutaneously into nude mice. HB-EGF is not directly mitogenic to endothelial cells but it induced the migration of bovine endothelial cells and release of endothelial cell mitogenic activity from bovine vascular SMC. This mitogenic activity was specifically blocked by neutralizing anti-vascular endothelial growth factor (VEGF) antibodies. In contrast, EGF or transforming growth factor-alpha (TGF-alpha) had almost no effect on release of endothelial mitogenicity from SMC. In addition, RT-PCR analysis demonstrated that VEGF165 mRNA levels were increased in vascular SMC 4-10-fold by 0.35-2 nM of HB-EGF, respectively. Our data suggest that HB-EGF, as a mediator of intercellular communication, may play a new important role in supporting wound healing, tumor progression and atherosclerosis by stimulating angiogenesis.
肝素结合表皮生长因子样生长因子（HB-EGF）是一种对血管平滑肌细胞（SMC）具有强大促有丝分裂作用和迁移作用的因子，可促进兔角膜体内新生血管形成。磁共振成像（MRI）定量显示了将HB-EGF皮下注射到裸鼠体内时的血管生成效应。HB-EGF对内皮细胞无直接促有丝分裂作用，但可诱导牛内皮细胞迁移，并从牛血管SMC释放内皮细胞促有丝分裂活性。这种促有丝分裂活性被中和性抗血管内皮生长因子（VEGF）抗体特异性阻断。相比之下，表皮生长因子（EGF）或转化生长因子-α（TGF-α）对SMC释放内皮促有丝分裂活性几乎没有影响。此外，逆转录-聚合酶链反应（RT-PCR）分析表明，0.35 - 2 nM的HB-EGF分别使血管SMC中的VEGF165 mRNA水平升高4 - 10倍。我们的数据表明，HB-EGF作为细胞间通讯的介质，可能通过刺激血管生成在支持伤口愈合、肿瘤进展和动脉粥样硬化方面发挥新的重要作用。
