Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cell s, and it promotes angiogenesis in vivo. Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG ) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effe ct was observed at 10-50 ng/ml for SCG and 100 ng/ml for DRG. VEGF-induced axonal outgrowth was inhibited by the mitogen-activated protein kinase kina se inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF a lso increased survival of both neurons and satellite cells and the number o f proliferating Schwann cells. Immunocytochemistry and immunoblotting revea led that VEGF was expressed in virtually all nerve cells in the SGG but onl y in a population of small-diameter (<35 mu m) neurons representing similar to 30% of the neurons in DRG. Immunostaining showed that the VEGF receptor fetal liver kinase receptor (flk-1) was found on nerve cell bodies in DRG and to a lesser extent on neurons in SCG. Growth cones of regenerating axon s from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwa nn cells. We conclude that VEGF has both neurotrophic and mitogenic activit y on cells in the peripheral nervous system.