Aquaporin-4 upregulated expression in glioma tissue is a reaction to glioma-associated edema induced by vascular endothelial growth factor

Glionia-associated edema contributes significantly to morbidity and death in patients with glioma. It has been suggested that vascular endothelial growth factor (VEGF) and aquaporin-4 (AQP4) play important roles in glioma-associated edema. However, the effect of VEGF on AQP4 expression is not clear. In this study, AQP4 expression was assayed in cultured glioma cells that express different amounts of VEGF, and AQP4 expression, vessel permeability and water content were assayed in glioma xenografts that express different amounts of VEGF. No difference in AQP4 expression was found between glioma cells expressing different VEGF amounts in vitro. However, AQP4 expression was increased in glioma tissue with increased VEGF, vessel permeability and water content. In conclusion, VEGF does not directly affect AQP-4 expression. The redistribution of AQP4 in glioblastoma cells is a reaction to vasogenic edema induced by VEGF for the purpose of facilitating reabsorption of excess fluid. The pattern of AQP4 expression in glioma provides new insights into the molecular changes occurring in glioma-associated edema and may help plan future therapeutic strategies.