Revealing the role of phospholipase C?3 in the regulation of VEGF-induced vascular permeability
- Authors
- 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.
- ID
- ZDB-PUB-120608-5
- 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
-
- Calcium Signaling/drug effects
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Animals
- Promoter Regions, Genetic/drug effects
- Cells, Cultured
- Endothelium, Vascular/cytology
- Endothelium, Vascular/drug effects
- Endothelium, Vascular/metabolism*
- Morpholinos/pharmacology
- Up-Regulation/drug effects
- Human Umbilical Vein Endothelial Cells/cytology
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/metabolism
- Capillary Permeability*/drug effects
- High-Throughput Screening Assays
- Humans
- Mice, Knockout
- HSP70 Heat-Shock Proteins/genetics
- HSP70 Heat-Shock Proteins/metabolism
- Vascular Endothelial Growth Factor A/antagonists & inhibitors
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism*
- Recombinant Proteins/antagonists & inhibitors
- Recombinant Proteins/metabolism
- Phospholipase C beta/antagonists & inhibitors
- Phospholipase C beta/genetics
- Phospholipase C beta/metabolism*
- Animals, Genetically Modified
- Heat-Shock Response
- Embryo, Nonmammalian
- Mice
- 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.