Dexamethasone coordinately regulates angiopoietin-1 and VEGF: A mechanism of glucocorticoid-induced stabilization of blood-brain barrier

Hyongbum Kim, Jung Min Lee, Jae Sun Park, Sangmee Ahn Jo, Yong Ou Kim, Chan Wha Kim, Inho Jo

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)243-248
Number of pages6
JournalBiochemical and biophysical research communications
Volume372
Issue number1
DOIs
Publication statusPublished - 2008 Jul 18

Keywords

  • Angiopoietin-1
  • Angiopoietin-2
  • Astrocytes
  • Blood-brain barrier
  • Dexamethasone
  • Endothelial cells
  • Glucocorticoids
  • Pericytes
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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