Fibroblast growth factor-2- mediated capillary morphogenesis of endothelial cells requires signals via Flt-1/vascular endothelial growth factor receptor-1: possible involvement of c-Akt.
Capillary morphogenesis is a crucial angiogenic response of endothelial cells. Although fibroblast growth factor-2 ( FGF-2) potently induces capillary morphogenesis, the contribution of vascular endothelial growth factor-A ( VEGF-A) in this response has not been clarified well. Here we examined the role of VEGF signaling in FGF-2- induced capillary morphogenesis by murine brain capillary endothelial cells (IBE cells) and human umbilical vein endothelial cells. FGF-2-treated IBE cells rapidly extended on Matrigel in association with actin reorganization. Chimeric protein, of which the extracellular domain of VEGF receptor-1 ( VEGFR-1) fused to immunoglobulin Fc, inhibited FGF-2-induced cell extension, resulting in decreased capillary morphogenesis. Blocking antibody against VEGFR-1 inhibited FGF-2-induced capillary formation. Also, anti- VEGF-A antibody inhibited FGF-2- induced capillary morphogenesis, which was restored by the addition of placental growth factor-1. Similar results were obtained by the experiments with human umbilical vein endothelial cells. Expression of kinase-inactive c-Akt in IBE cells showed impaired capillary morphogenesis promoted by FGF-2. Conversely, stable cell lines expressing activated c-Akt demonstrated ligand-independent capillaries, which were resistant to the treatment with anti-VEGFR-1 blocking antibody. Upstream of c-Akt, calmodulin-dependent signals seemed to be involved. Taken together, signals via VEGFR-1 were required for FGF-2- induced capillary morphogenesis by endothelial cells, and c-Akt activity seemed to be involved in this process.[1]References
- Fibroblast growth factor-2-mediated capillary morphogenesis of endothelial cells requires signals via Flt-1/vascular endothelial growth factor receptor-1: possible involvement of c-Akt. Kanda, S., Miyata, Y., Kanetake, H. J. Biol. Chem. (2004) [Pubmed]
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