Zinc-finger transcriptional factor Sall1 induces angiogenesis by activation of the gene for VEGF-A.
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.
Yamamoto
Chii
C
Advanced Research Institute of Science and Humanities, Nihon University, Tokyo, Japan.
Fukuda
Noboru
N
Matsumoto
Taro
T
Higuchi
Terumi
T
Ueno
Takahiro
T
Matsumoto
Koichi
K
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C104146:SALL1 protein, human; C491254:Sall1 protein, mouse; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A