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- Title
SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier.
- Authors
Lee, Sae-Won; Kim, Woo Jean; Choi, Yoon Kyung; Song, Hyun Seok; Son, Myung Jin; Gelman, Irwin H.; Kim, Yung-Jin; Kim, Kyu-Won
- Abstract
The blood-brain barrier (BBB) is essential for maintaining brain homeostasis and low permeability. BBB maintenance is important in the central nervous system (CNS) because disruption of the BBB may contribute to many brain disorders, including Alzheimer disease and ischemic stroke. The molecular mechanisms of BBB development remain ill-defined, however. Here we report that src-suppressed C-kinase substrate (SSeCKS) decreases the expression of vascular endothelial growth factor (VEGF) through AP-1 reduction and stimulates expression of angiopoietin-1 (Ang-1), an antipermeability factor in astrocytes. Conditioned media from SSeCKS-overexpressing astrocytes (SSeCKS-CM) blocked angiogenesis in vivo and in vitro. Moreover, SSeCKS-CM increased tight junction proteins in endothelial cells, consequently decreasing [³H]sucrose permeability. Furthermore, immunoreactivity to SSeCKS gradually increased during the BBB maturation period, and SSeCKS-expressing astrocytes closely interacted with zonula occludens (ZO)-1-expressing blood vessels in vivo. Collectively, our results suggest that SSeCKS regulates BBB differentiation by modulating both brain angiogenesis and tight junction formation.
- Subjects
BLOOD-brain barrier; NEOVASCULARIZATION; TIGHT junctions; BRAIN diseases
- Publication
Nature Medicine, 2003, Vol 9, Issue 7, p900
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm889