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Victor H Guaiquil, Yun-Cin Luo, Joy Sarkar, Mark Rosenblatt; Mechanistic studies for Vascular Endothelial Growth Factor-A and -B induced neuronal and endothelial cell growth. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3524.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the mechanisms of VEGF-induced endothelial and neuronal cell growth
To characterize the mechanisms by which VEGF-A and VEGF-B induced cornea nerve regeneration and angiogenesis, we treated isolated trigeminal ganglia (TG) neuronal cells from Thy1-YFP mice and rat PC12 neuronal cell line with VEGF-A and -B and analyzed the neurite- induced growth in a time and dose dependent manner. We performed Western blot, immunoprecipitation (IP) and mass cytometry analysis to determine the receptor-ligand interactions induced by both growth factors in endothelial and neuronal cells.
Both VEGF-A and VEGF-B induced neuronal growth in isolated trigeminal ganglia neurons as well as in PC12 cells. VEGF-A induced mostly TG neurite elongation while VEGF-B induced increased neurite branching. Western blot analysis shows that VEGF receptor 1 (R1) and Neuropilin 1 (NRP1) are highly expressed in the neuronal PC12 cells compared to mouse endothelial cells of vein or artery origin. The levels of VEGFR2 were similar in all cell lines studied. The IP studies showed that VEGFR1 heterodimerize with VEGFR2 in PC12 cells and the level of expression increases upon VEGF-A or -B treatment. Mass cytometry analysis showed that in endothelial cells the surface expression of VEGFR1, VEGFR2 and NRP1 increased upon VEGF-A or –B treatment, while VGFR1 seems to be internalized in PC12 cells.
VEGF-A and -B can selectively and potently enhance neurite growth, but only VEGFA is a potent inducer of angiogenesis. Since both processes use similar receptors we are beginning to characterize the differences that occur in each type of cells upon ligand binding. Further studies will reveal where the regulation of these pathways diverge to induced specific cellular growth.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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