Heparin-binding epidermal growth factor-like growth factor (HB-EGF) a patent mitogen and migration factor for vascular smooth muscle cells (SMC), promoted neovascularization in vivo in the rabbit cornea. MRI demonstrated quantitatively tile 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-α. (TGF-α) had almost no effect on release of endothelial mitogenicity from SMC. In addition, RT-PCR analysis demonstrated that VEGF165 mRNA levels mere increased in vascular SMC 4-10-fold by 0.35-2 nM of HB-EGP, 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.
Bibliographical noteFunding Information:
This work was supported by a grant from the Chief Scientist of the Israel Ministry of Health (to M.M. and M.N.), by a Research Career Development Award from the Israel Cancer Research Fund (to M.N.) and by a grant from The Israel Science Foundation (to M.N.). M.N. is the incumbent of the Dr. Phil Gold Career Development Chair in Cancer Research. R.A. is a recipient of a fellowship from the Charles Clore foundation.
- Endothelial cell
- Heparin-binding epidermal growth factor-like growth factor
- Vascular endothelial growth factor
- Vascular smooth msucle cell