RT Journal Article SR Electronic T1 Verge: A Novel Vascular Early Response Gene JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 4092 OP 4103 DO 10.1523/JNEUROSCI.4252-03.2004 VO 24 IS 16 A1 Jean B. Regard A1 Sigrid Scheek A1 Talaibek Borbiev A1 Anthony A. Lanahan A1 Armin Schneider A1 Anna-Maria Demetriades A1 Holger Hiemisch A1 Carol A. Barnes A1 Alexander D. Verin A1 Paul F. Worley YR 2004 UL http://www.jneurosci.org/content/24/16/4092.abstract AB Vascular endothelium forms a continuous, semipermeable barrier that regulates the transvascular movement of hormones, macromolecules, and other solutes. Here, we describe a novel immediate early gene that is expressed selectively in vascular endothelial cells, verge (vascular early response gene). Verge protein includes an N-terminal region of ∼70 amino acids with modest homology (∼30% identity) to Apolipoprotein L but is otherwise unique. Verge mRNA and protein are induced selectively in the endothelium of adult vasculature by electrical or chemical seizures. Verge expression appears to be responsive to local tissue conditions, because it is induced in the hemisphere ipsilateral to transient focal cerebral ischemia. In contrast to the transient expression in adult, Verge mRNA and protein are constitutively expressed at high levels in the endothelium of developing tissues (particularly heart) in association with angiogenesis. Verge mRNA is induced in cultured endothelial cells by defined growth factors and hypoxia. Verge protein is dramatically increased by cysteine proteinase inhibitors, suggesting rapid turnover, and is localized to focal regions near the periphery of the cells. Endothelial cell lines that stably express Verge form monolayers that show enhanced permeability in response to activation of protein kinase C by phorbol esters. This response is accompanied by reorganization of the actin cytoskeleton and the formation of paracellular gaps. These studies suggest that Verge functions as a dynamic regulator of endothelial cell signaling and vascular function.