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The Journal of Neuroscience, July 15, 1999, 19(14):5731-5740
Vascular Endothelial Growth Factor Has Neurotrophic Activity and Stimulates Axonal Outgrowth, Enhancing Cell Survival and Schwann Cell Proliferation in the Peripheral Nervous System
Mariann Sondell1, Göran Lundborg2, and Martin Kanje1 1 Department of Animal Physiology, University of Lund, S-223 62 Lund, Sweden, and 2 Department of Hand Surgery, Malmö General Hospital, University of Lund, S-20502 Malmö, Sweden
Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells, and it promotes angiogenesis in vivo. Here we report that VEGF165 has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effect 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 kinase inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF also increased survival of both neurons and satellite cells and the number of proliferating Schwann cells. Immunocytochemistry and immunoblotting revealed that VEGF was expressed in virtually all nerve cells in the SCG but only in a population of small-diameter (<35 µm) neurons representing ~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 axons from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwann cells. We conclude that VEGF has both neurotrophic and mitogenic activity on cells in the peripheral nervous system.
Key words: axonal outgrowth; DRG; growth factor; mouse; nerve regeneration; peripheral nerve; SCG; VEGF
Copyright © 1999 Society for Neuroscience 0270-6474/99/19145731-10$05.00/0
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