A Critical Role for Phosphatidylinositol (3,4,5)-Trisphosphate–Dependent Rac Exchanger 1 in Endothelial Junction Disruption and Vascular Hyperpermeability

Abstract

These results demonstrate for the first time that P-Rex1 expressed in endothelial cells is activated downstream of TNF-α, which is not a G protein-coupled receptor agonist. Our data identify P-Rex1 as a critical mediator of vascular barrier disruption. Targeting P-Rex1 may effectively protect against TNF-α- and lipopolysaccharide-induced endothelial junction disruption and vascular hyperpermeability.