Journal
BLOOD
Volume 120, Issue 11, Pages 2167-2173Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-03-417824
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Funding
- National Institutes of Health [HL70567, CA78383, CA150190]
- Bruce and Martha Atwater Foundation
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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 knockdown and knockout mice, we describe a novel role of phospholipase C beta 3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLC beta 3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes. (Blood. 2012;120(11):2167-2173)
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