Dexamethasone coordinately regulates angiopoietin-1 and VEGF: a mechanism of glucocorticoid-induced stabilization of blood-brain barrier.
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.
Kim
Hyongbum
H
Department of Biomedical Sciences, National Institute of Health, Seoul, South Korea.
Lee
Jung Min
JM
Park
Jae Sun
JS
Jo
Sangmee Ahn
SA
Kim
Yong-Ou
YO
Kim
Chan-Wha
CW
Jo
Inho
I
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D042683:Angiopoietin-1; D005938:Glucocorticoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D015735:Mifepristone; D003907:Dexamethasone