Dexamethasone coordinately regulates angiopoietin-1 and VEGF: A mechanism of glucocorticoid-induced stabilization of blood-brain barrier
- Authors
- Kim, Hyongbum; Lee, Jung Min; Park, Jae Sun; Jo, Sangmee Ahn; Kim, Yong-Ou; Kim, Chan-Wha; Jo, Inho
- Issue Date
- 18-7월-2008
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- glucocorticoids; dexamethasone; endothelial cells; astrocytes; pericytes; blood-brain barrier; vascular endothelial growth factor; angiopoietin-1; angiopoietin-2
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.372, no.1, pp.243 - 248
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 372
- Number
- 1
- Start Page
- 243
- End Page
- 248
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/123019
- DOI
- 10.1016/j.bbrc.2008.05.025
- ISSN
- 0006-291X
- 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-incluced 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. (C) 2008 Elsevier Inc. All rights reserved.
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