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 language | English |
|---|---|
| Pages (from-to) | 243-248 |
| Number of pages | 6 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 372 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2008 Jul 18 |
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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 journal › Article
}
TY - JOUR
T1 - Dexamethasone coordinately regulates angiopoietin-1 and VEGF
T2 - A mechanism of glucocorticoid-induced stabilization of blood-brain barrier
AU - Kim, Hyongbum
AU - Lee, Jung Min
AU - Park, Jae Sun
AU - Jo, Sangmee Ahn
AU - Kim, Yong Ou
AU - Kim, Chan Wha
AU - Jo, Inho
PY - 2008/7/18
Y1 - 2008/7/18
N2 - 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.
AB - 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.
KW - Angiopoietin-1
KW - Angiopoietin-2
KW - Astrocytes
KW - Blood-brain barrier
KW - Dexamethasone
KW - Endothelial cells
KW - Glucocorticoids
KW - Pericytes
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=44649139796&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44649139796&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.05.025
DO - 10.1016/j.bbrc.2008.05.025
M3 - Article
VL - 372
SP - 243
EP - 248
JO - The BMJ
JF - The BMJ
SN - 0730-6512
IS - 1
ER -