Premium
Role of vasodilator stimulated phosphoprotein in VEGF induced blood–brain barrier permeability in endothelial cell monolayers
Author(s) -
Davis Brandon,
Tang Jun,
Zhang Li,
Mu Dezhi,
Jiang Xiangning,
Biran Valerie,
Vexler Zinaida,
Ferriero Donna M.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.06.010
Subject(s) - blood–brain barrier , angiogenesis , vascular permeability , microbiology and biotechnology , tight junction , vascular endothelial growth factor , hypoxia (environmental) , endothelial stem cell , phosphorylation , chemistry , cancer research , biology , endocrinology , central nervous system , in vitro , biochemistry , vegf receptors , organic chemistry , oxygen
Abstract The blood–brain barrier (BBB) plays an important role in the pathophysiology of central nervous system (CNS) disorders such as stroke and hypoxic–ischemic brain injury. Vascular endothelial growth factor (VEGF) is involved in angiogenesis and vasogenic edema during stroke and hypoxia. However, the role of VEGF in BBB permeability after hypoxia has not been fully elucidated. We therefore investigated VEGF effects in an in vitro BBB model using rbcec4 endothelial cell line with the stimulation of VEGF or hypoxia. In this study, BBB permeability was studied using 14 C‐sucrose detection. The expression of BBB tight junction protein ZO‐1, and the expression and phosphorylation of vasodilator stimulated phosphoprotein (VASP), VEGF and VEGF receptor 2 (VEGFR2) were determined using fluorescent immunocytochemistry and western blot analyses. We found that hypoxia upregulated VEGF expression, and VEGF increased BBB permeability. Hypoxia also increased VASP phosphorylation, which was mediated, in part, through VEGFR2. We also found that VASP at tight junctions was co‐localized with ZO‐1 in cell–cell contacts. Our findings show that VASP phosphorylation is affected by hypoxia and VEGFR2 inhibition suggesting a role for VASP in BBB permeability.