ZFIN ID: ZDB-PUB-120608-5
Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability
Hoeppner, L.H., Phoenix, K.N., Clark, K.J., Bhattacharya, R., Gong, X., Sciuto, T.E., Vohra, P., Suresh, S., Bhattacharya, S., Dvorak, A.M., Ekker, S.C., Dvorak, H.F., Claffey, K.P., and Mukhopadhyay, D.
Date: 2012
Source: Blood 120(11): 2167-2173 (Journal)
Registered Authors: Clark, Karl, Ekker, Stephen C., Gong, Xun, Hoeppner, Luke, Mukhopadhyay, Debabrata
Keywords: none
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Calcium Signaling/drug effects
  • Capillary Permeability*/drug effects
  • Cells, Cultured
  • Embryo, Nonmammalian
  • Endothelium, Vascular/cytology
  • Endothelium, Vascular/drug effects
  • Endothelium, Vascular/metabolism*
  • HSP70 Heat-Shock Proteins/genetics
  • HSP70 Heat-Shock Proteins/metabolism
  • Heat-Shock Response
  • High-Throughput Screening Assays
  • Human Umbilical Vein Endothelial Cells/cytology
  • Human Umbilical Vein Endothelial Cells/drug effects
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Morpholinos/pharmacology
  • Phospholipase C beta/antagonists & inhibitors
  • Phospholipase C beta/genetics
  • Phospholipase C beta/metabolism*
  • Promoter Regions, Genetic/drug effects
  • Recombinant Proteins/antagonists & inhibitors
  • Recombinant Proteins/metabolism
  • Up-Regulation/drug effects
  • Vascular Endothelial Growth Factor A/antagonists & inhibitors
  • Vascular Endothelial Growth Factor A/genetics
  • Vascular Endothelial Growth Factor A/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 22674805 Full text @ Blood

Vascular endothelial growth factor A (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. We report a heat-inducible VEGF transgenic zebrafish model through which VP can be monitored in real-time. Using this approach with morpholino-mediated gene knockdown, as well as knockout mice, we describe a novel role of phospholipase Cβ3 as a negative regulator of VEGF-mediated VP by regulating intracellular calcium release. Our results suggest an important function of PLCβ3 on VP and also present a new model to identify genetic regulators of VP crucial to several disease processes.