He, PingPhilbrick, Melissa J.An, XiaojinWu, JiapingMessmer-Blust, Angela F.Li, Jian2014-03-112014He, Ping, Melissa J. Philbrick, Xiaojin An, Jiaping Wu, Angela F. Messmer-Blust, and Jian Li. 2014. “Endothelial Differentiation Gene-1, a New Downstream Gene Is Involved in RTEF-1 Induced Angiogenesis in Endothelial Cells.” PLoS ONE 9 (2): e88143. doi:10.1371/journal.pone.0088143. http://dx.doi.org/10.1371/journal.pone.0088143.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879844Related 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.en-USBiologyGeneticsGene ExpressionGene FunctionMolecular Cell BiologyDNA transcriptionRNA interferenceSignal TransductionSignaling in Cellular ProcessesG-Protein SignalingCell GrowthMedicineCardiovascularVascular BiologyJournal Article2014-03-1110.1371/journal.pone.0088143