Metallothionein 1 is a Downstream Target of Vascular Endothelial Zinc Finger 1 (VEZF1) in Endothelial Cells and Participates in the Regulation of Angiogenesis

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.