Metallothionein 1 is a downstream target of vascular endothelial zinc finger 1 (VEZF1) in endothelial cells and participates in the regulation of angiogenesis

Metallothionein 1 is a downstream target of vascular endothelial zinc finger 1 (VEZF1) in endothelial cells and participates in the regulation of angiogenesis
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DOI:
10.1080/10623320500227101
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发表时间:
2005-07-01
影响因子:
--
通讯作者:
Sato, Y
Sato, Y
中科院分区:
其他
文献类型:
--
作者:
Miyashita, H;Sato, Y

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血管内皮锌指1 (Vascular endothelial zinc finger 1, VEZF1)是一种在内皮细胞中表达的转录因子,在血管生成的调控中起着必不可少的作用。作者先前的微阵列分析显示,VEZF1基因的下调导致内皮细胞金属硫蛋白1 (metallothionein 1, MT1)基因的减少。Northern blotting结果显示,内皮细胞中,VEZF1下调表达减少,而VEZF1上调表达增加。此外,MT1在体内血管生成部位的内皮细胞中表达。因此,作者研究了MT1是否在血管生成的调节中发挥任何作用。内皮细胞中MT1的下调抑制了体外增殖、迁移和网络形成,以及体内血管生成。此外,MT1的下调导致细胞周期阻滞在G1期。这些结果表明,MT1是内皮细胞中VEZF1的下游靶点,并参与血管生成的调节。
Vascular endothelial zinc finger 1 (VEZF1) is a transcription factor that is expressed in endothelial cells and plays a requisite role in the regulation of angiogenesis. The authors' previous microarray analysis revealed that the down-regulation of VEZF1 gene resulted in the decrease of metallothionein 1 (MT1) gene in endothelial cells. Here the authors showed by Northern blotting that the down-regulation of VEZF1 decreased, whereas up-regulation of VEZF1 increased, the expression of MT1 in endothelial cells. Moreover, MT1 was expressed in endothelial cells at the site of angiogenesis in vivo. The authors therefore examined whether MT1 played any role in the regulation of angiogenesis. Down-regulation of MT1 in endothelial cells inhibited proliferation, migration, and network formation in vitro, as well as angiogenesis in vivo. Moreover, down-regulation of MT1 resulted in the cell cycle arrest at G1 phase. These results indicate that MT1 is a downstream target of VEZF1 in endothelial cells and is involved in the regulation of angiogenesis.