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

Luke H. Hoeppner, Kathryn N. Phoenix, Karl J. Clark, Resham Bhattacharya, Xun Gong, Tracey E. Sciuto, Pawan Vohra, Sandip Suresh, Santanu Bhattacharya, Ann M. Dvorak, Stephen C. Ekker, Harold F. Dvorak, Kevin P. Claffey, Debabrata Mukhopadhyay

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19 Scopus citations

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 knockdown 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.

Original languageEnglish (US)
Pages (from-to)2167-2173
Number of pages7
JournalBlood
Volume120
Issue number11
DOIs
StatePublished - Sep 13 2012

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    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., & Mukhopadhyay, D. (2012). Revealing the role of phospholipase Cβ3 in the regulation of VEGF-induced vascular permeability. Blood, 120(11), 2167-2173. https://doi.org/10.1182/blood-2012-03-417824