Endothelial differentiation gene-1, a new downstream gene is involved in RTEF-1 induced angiogenesis in endothelial cells

• Published in: PloS one 2014-02, Vol.9 (2), p.e88143
• Main Authors: He, Ping, Philbrick, Melissa J, An, Xiaojin, Wu, Jiaping, Messmer-Blust, Angela F, Li, Jian
• Format: Article
• Language: English
• Subjects: Agglomeration; Angiogenesis; Animals; Biology; Cell adhesion & migration; Cell aggregation; Cell Aggregation - drug effects; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Differentiation; DNA-Binding Proteins - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium; Gene expression; Gene Expression Regulation - drug effects; Genes; Growth factors; HEK293 Cells; Humans; Hypoxia; Laboratory animals; Medical schools; Medicine; Mice; Microvasculature; Muscle Proteins - metabolism; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - genetics; Pertussis; Pertussis toxin; Pertussis Toxin - pharmacology; Proteins; Receptors, Lysosphingolipid - genetics; Receptors, Lysosphingolipid - metabolism; Rodents; siRNA; Skin; Smooth muscle; Transcription factors; Transcription Factors - metabolism; Transgenic animals
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088143

Related Transcriptional Enhancer Factor-1 (RTEF-1) has been suggested to induce angiogenesis through regulating target genes. Whether RTEF-1 has a direct role in angiogenesis and what specific genes are involved in RTEF-1 driven angiogenisis have not been elucidated. We found that over-expressing RTEF-1 in Human dermal microvascular endothelial cells-1 (HMEC-1) significantly increased endothelial cell aggregation, growth and migration while the processes were inhibited by siRNA of RTEF-1. In addition, we observed that Endothelial differentiation gene-1 (Edg-1) expression was up-regulated by RTEF-1 at the transcriptional level. RTEF-1 could bind to Edg-1 promoter and subsequently induce its activity. Edg-1 siRNA significantly blocked RTEF-1-driven increases in endothelial cell aggregation in a Matrigel assay and retarded RTEF-1-induced endothelial cell growth and migration. Pertussis Toxin (PTX), a Gi/Go protein sensitive inhibitor, was found to inhibit RTEF-1 driven endothelial cell aggregation and migration. Our data demonstrates that Edg-1 is a potential target gene of RTEF-1 and is involved in RTEF-1-induced angiogenesis in endothelial cells. Gi/Go protein coupled receptor pathway plays a role in RTEF-1 driven angiogenesis in endothelial cells.