Zinc-finger transcriptional factor Sall1 induces angiogenesis by activation of the gene for VEGF-A
Zinc-finger transcriptional factor Sall1 induces angiogenesis by activation of the gene for VEGF-A
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DOI：
10.1038/hr.2009.195
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发表时间：
2010-02
影响因子：
5.4
通讯作者：
C. Yamamoto;N. Fukuda;Taro Matsumoto;T. Higuchi;T. Ueno;Koichi Matsumoto
中科院分区：
文献类型：
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作者：
C. Yamamoto;N. Fukuda;Taro Matsumoto;T. Higuchi;T. Ueno;Koichi Matsumoto
锌指转录因子Sall 1调节基因表达并调节器官发生，包括肾脏发育。由血管内皮生长因子（VEGF）诱导的血管生成也是器官发生所必需的。我们研究了Sall 1是否通过VEGF基因激活诱导血管生成。Sall 1基因转移诱导大鼠角膜和小鼠胚状体（EBs）中显著的新生血管形成。抗VEGF抗体可阻断EB的新生血管形成。Sall 1基因转染Swiss 3 T3细胞后，VEGF-A mRNA的表达明显增加，而成纤维细胞生长因子-2、表皮生长因子、肝细胞生长因子和ETS-1 mRNA的表达无明显增加。Sall 1基因转移显著增加了培养成纤维细胞条件培养基中VEGF-A蛋白水平。与转染模拟载体或截短的Sall 1的细胞相比，Sall 1基因转染显著增加HEK 293 T细胞中VEGF-A启动子活性。这些结果表明，Sall 1通过刺激VEGF-A启动子活性诱导血管生成。
Zinc-finger transcriptional factor Sall1 modulates gene expression and regulates organogenesis, including kidney development. Angiogenesis induced by vascular endothelial growth factor (VEGF) is also required for organogenesis. We investigated whether Sall1 induces angiogenesis through VEGF gene activation. Sall1 gene transfer induced marked neovascularization in rat cornea and in mouse embryoid bodies (EBs). The neovascularization in EBs was abolished by co-administration of anti-VEGF antibody. Sall1 gene transfer in Swiss 3T3 cells significantly increased the expression of VEGF-A mRNA but did not markedly increase the expression of fibroblast growth factor-2, epidermal growth factor, hepatocyte growth factor and ETS-1 mRNA. Sall1 gene transfer significantly increased VEGF-A protein levels in conditioned medium from cultured fibroblasts. Sall1 gene transfer significantly increased VEGF-A promoter activity in HEK293T cells as compared with cells transfected with mock vector or truncated Sall1. These results suggest that Sall1 induces angiogenesis by stimulating VEGF-A promoter activity.