title: Sonic hedgehog (Shh) regulates the expression of angiogenic growth factors in oxygen-glucose-deprived astrocytes by mediating the nuclear receptor NR2F2.
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.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors: Yanan
authors: Y
authors: Li
authors: Yuanpeng
authors: Y
authors: Xia
authors: Yong
authors: Y
authors: Wang
authors: Ling
authors: L
authors: Mao
authors: Yuan
authors: Y
authors: Gao
authors: Quanwei
authors: Q
authors: He
authors: Ming
authors: M
authors: Huang
authors: Shengcai
authors: S
authors: Chen
authors: Bo
authors: B
authors: Hu
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D053823:Hedgehog Proteins / Q000494:pharmacology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D051837:COUP Transcription Factor II; C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D000071676:Zinc Finger Protein GLI1; D005947:Glucose; D010100:Oxygen
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