Abstract
Sonic hedgehog (Shh) has been found to regulate the angiogenic growth factor such as VEGF, Ang-1, and Ang-2 during ischemic insults, but the underlying mechanism is not fully understood. In this study, we employed oxygen–glucose deprivation (OGD) in astrocytes to mimic the ischemia in vitro. We found that OGD could induce the expressions of VEGF, Ang-1, and Ang-2, with the expression of Shh signaling components increased. Moreover, inhibiting the Shh signaling pathway with 5EI, a specific antibody, could decrease the expressions of VEGF, Ang-1, and Ang-2. Furthermore, the administration of exogenous Shh could induce the expressions of VEGF, Ang-1, and Ang-2 in astrocytes. The results of silencing Gli-1, or NR2F2, exhibited that exogenous Shh could regulate the expressions of VEGF, Ang-1, and Ang-2 in astrocytes by activating the NR2F2, but not the Gli-1. These results suggested that Shh could regulate the angiogenic growth factor after ischemic insults in astrocytes, and the regulation was partially mediated by the NR2F2.
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Acknowledgments
This work was supported by grant 81070938 from the Program of National Natural Science Foundation of China (to BH), grant 81101905 from the Program of National Natural Science Foundation of China (to LM), New Century Excellent Talents in University NCET-10-0406 (to BH), and the Fundamental Research Funds for the Central Universities, HUST no.2010JC028 (to BH).
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Yanan Li and Yuanpeng Xia contributed equally to this project.
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Li, Y., Xia, Y., Wang, Y. et al. Sonic Hedgehog (Shh) Regulates the Expression of Angiogenic Growth Factors in Oxygen–Glucose-Deprived Astrocytes by Mediating the Nuclear Receptor NR2F2. Mol Neurobiol 47, 967–975 (2013). https://doi.org/10.1007/s12035-013-8395-9
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DOI: https://doi.org/10.1007/s12035-013-8395-9