Verge: A Novel Vascular Early Response Gene

Jean B. Regard, Sigrid Scheek, Talaibek Borbiev, Anthony A. Lanahan, Armin Schneider, Anna Maria Demetriades, Holger Hiemisch, Carol A. Barnes, Alexander D. Verin, Paul F. Worley

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4092-4103
Number of pages12
JournalJournal of Neuroscience
Volume24
Issue number16
DOIs
StatePublished - Apr 21 2004

Keywords

  • ECIS
  • Electrical cell-substrate impedance sensing
  • Endothelial cell
  • IEG
  • Immediate early gene
  • Ischemia
  • MCAO
  • Middle cerebral artery occlusion
  • PKC
  • Protein kinase C
  • Seizure
  • Stroke model
  • TER
  • Transendothelial resistance
  • Vascular permeability

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Regard, J. B., Scheek, S., Borbiev, T., Lanahan, A. A., Schneider, A., Demetriades, A. M., Hiemisch, H., Barnes, C. A., Verin, A. D., & Worley, P. F. (2004). Verge: A Novel Vascular Early Response Gene. Journal of Neuroscience, 24(16), 4092-4103. https://doi.org/10.1523/JNEUROSCI.4252-03.2004