Revealing the role of phospholipase C3 in the regulation of VEGF-induced vascular permeability. uri icon

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 C3 as a negative regulator of VEGF-mediated VP by regulating intracellular Ca2+ release. Our results suggest an important effect of PLC3 on VP and provide a new model with which to identify genetic regulators of VP crucial to several disease processes.

published proceedings

  • Blood

author list (cited authors)

  • Hoeppner, L. H., Phoenix, K. N., Clark, K. J., Bhattacharya, R., Gong, X., Sciuto, T. E., ... Mukhopadhyay, D.

complete list of authors

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

publication date

  • September 2012

published in