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

74 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

Fingerprint

Angiopoietin-1
Blood-Brain Barrier
Dexamethasone
Vascular Endothelial Growth Factor A
Glucocorticoids
Stabilization
Angiopoietin-2
Messenger RNA
Endothelial cells
Brain
Endothelial Cells
Pericytes
Proteins
Brain Edema
Glucocorticoid Receptors
RNA Stability
Astrocytes
Permeability
Hormones

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Dexamethasone coordinately regulates angiopoietin-1 and VEGF : A mechanism of glucocorticoid-induced stabilization of blood-brain barrier. / Kim, Hyongbum; Lee, Jung Min; Park, Jae Sun; Jo, Sangmee Ahn; Kim, Yong Ou; Kim, Chan Wha; Jo, Inho.

In: Biochemical and Biophysical Research Communications, Vol. 372, No. 1, 18.07.2008, p. 243-248.

Research output: Contribution to journalArticle

Kim, Hyongbum ; Lee, Jung Min ; Park, Jae Sun ; Jo, Sangmee Ahn ; Kim, Yong Ou ; Kim, Chan Wha ; Jo, Inho. / Dexamethasone coordinately regulates angiopoietin-1 and VEGF : A mechanism of glucocorticoid-induced stabilization of blood-brain barrier. In: Biochemical and Biophysical Research Communications. 2008 ; Vol. 372, No. 1. pp. 243-248.
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