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Dexamethasone coordinately regulates angiopoietin-1 and VEGF: A mechanism of glucocorticoid-induced stabilization of blood-brain barrier
- Dexamethasone coordinately regulates angiopoietin-1 and VEGF: A mechanism of glucocorticoid-induced stabilization of blood-brain barrier
- Kim H.; Lee J.M.; Park J.S.; Jo S.A.; Kim Y.-O.; Kim C.-W.; Jo I.
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- Biochemical and Biophysical Research Communications
- vol. 372, no. 1, pp. 243 - 248
- SCI; SCIE; SCOPUS
- Glucocorticoids stabilize the blood-brain barrier (BBB), leading to attenuation of vasogenic brain edema. However, the action mechanism of glucocorticoids has been poorly elucidated. To elucidate the mechanism, we investigated whether dexamethasone (Dex), a synthetic glucocorticoid hormone, regulates the levels of key permeability regulating factors such as angiopoietin-1, angiopoietin-2, and vascular endothelial growth factor (VEGF) in the three types of cells comprising BBB. Dex increased the level of angiopoietin-1 mRNA and protein and decreased VEGF mRNA and protein in brain astrocytes and pericytes, but not in endothelial cells. The mRNA and protein of angiopoietin-2 were detected only in endothelial cells and not regulated by Dex. The Dex-induced regulation of angiopoietin-1 and VEGF was inhibited by RU486, suggestive of glucocorticoid receptor mediation. The mRNA stability of angiopoietin-1 and VEGF was not changed by Dex treatment, implying that Dex increases angiopoietin-1 and decreases VEGF through transcriptional regulation. This is the first study showing the coordinate regulation of angiopoietin-1 and VEGF by glucocorticoids, suggesting a novel mechanism underlying glucocorticoids-induced stabilization of BBB. © 2008 Elsevier Inc. All rights reserved.
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