Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability.

Publication Type:

Journal Article

Source:

Blood, Volume 120, Issue 11, p.2167-73 (2012)

Keywords:

Animalsdigestive disease, digestive deseases Animals, Genetically Modifieddigestive disease, digestive deseases Calcium Signalingdigestive disease, digestive deseases Capillary Permeabilitydigestive disease, digestive deseases Cells, Cultureddigestive disease, digestive deseases Embryo, Nonmammaliandigestive disease, digestive deseases Endothelium, Vasculardigestive disease, digestive deseases Heat-Shock Responsedigestive disease, digestive deseases High-Throughput Screening Assaysdigestive disease, digestive deseases HSP70 Heat-Shock Proteinsdigestive disease, digestive deseases Human Umbilical Vein Endothelial Cellsdigestive disease, digestive deseases Humansdigestive disease, digestive deseases Micedigestive disease, digestive deseases Mice, Knockoutdigestive disease, digestive deseases Morpholinosdigestive disease, digestive deseases Phospholipase C betadigestive disease, digestive deseases Promoter Regions, Geneticdigestive disease, digestive deseases Recombinant Proteinsdigestive disease, digestive deseases Up-Regulationdigestive disease, digestive deseases Vascular Endothelial Growth Factor Adigestive disease, digestive deseases Zebrafishdigestive disease, digestive deseases Zebrafish Proteins

Abstract:

VEGF induces vascular permeability (VP) in ischemic diseases and cancer, leading to many pathophysiological consequences. The molecular mechanisms by which VEGF acts to induce hyperpermeability are poorly understood and in vivo models that easily facilitate real-time, genetic studies of VP do not exist. In the present study, we report a heat-inducible VEGF transgenic zebrafish (Danio rerio) model through which VP can be monitored in real time. Using this approach with morpholino-mediated gene knock-down and knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLCβ3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.