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Astrocyte-Derived Sonic Hedgehog Contributes to Angiogenesis in Brain Microvascular Endothelial Cells via RhoA/ROCK Pathway After Oxygen-Glucose Deprivation.
MedLine Citation:
PMID:  23325464     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The human adult brain possesses intriguing plasticity, including neurogenesis and angiogenesis, which may be mediated by the activated sonic hedgehog (Shh). By employing a coculture system, brain microvascular endothelial cells (BMECs) cocultured with astrocytes, which were incubated under oxygen-glucose deprivation (OGD) condition, we tested the hypothesis that Shh secreted by OGD-activated astrocytes promotes cerebral angiogenesis following ischemia. The results of this study demonstrated that Shh was mainly secreted by astrocytes and the secretion was significantly upregulated after OGD. The proliferation, migration, and tube formation of BMECs cocultured with astrocytes after OGD were significantly enhanced, but cyclopamine (a Shh antagonist) or 5E1 (an antibody of Shh) reversed the change. Furthermore, silencing Ras homolog gene family, member A (RhoA) of BMECs by RNAi and blocking Rho-dependent kinase (ROCK) by Y27632, a specific antagonist of ROCK, suppressed the upregulation of proliferation, migration, and tube formation of BMECs after OGD. These findings suggested that Shh derived from activated astrocytes stimulated RhoA/ROCK pathway in BMECs after OGD, which might be involved in angiogenesis in vitro.
Authors:
Quan-Wei He; Yuan-Peng Xia; Sheng-Cai Chen; Yong Wang; Ming Huang; Yan Huang; Jian-Yong Li; Ya-Nan Li; Yuan Gao; Ling Mao; Yuan-Wu Mei; Bo Hu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-17
Journal Detail:
Title:  Molecular neurobiology     Volume:  -     ISSN:  1559-1182     ISO Abbreviation:  Mol. Neurobiol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8900963     Medline TA:  Mol Neurobiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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