Placental growth factor induces FosB and c-Fos gene expression via Flt-1 receptors.
Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that binds specifically to Flt-1. The biological roles of PlGF and Flt-1 have not yet been defined and the signalling mechanisms mediating cellular actions of PlGF remain poorly understood. In human umbilical vein endothelial cells, VEGF and PlGF induced expression of both full-length FosB mRNA and an alternatively spliced variant, DeltaFosB, with similar efficacy and kinetics. In contrast, PlGF induced c-Fos expression less strongly than VEGF, and whereas VEGF strongly upregulated tissue factor mRNA, PlGF had a negligible effect. PlGF induced c-Fos expression in porcine aortic endothelial cells specifically expressing Flt-1, and FosB expression in the monocytic RAW 264.7 cell line expressing endogenous Flt-1. These findings show for the first time that VEGF and PlGF induce mRNA expression of the transcription factors FosB and c-Fos, and suggest that these factors may play a role in the biological responses mediated by PlGF and Flt-1.
Holmes
David I R
DI
Department of Medicine, The Rayne Building, University College London, 5 University Street, London WC1E 6JJ, UK.
Zachary
Ian
I
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D014644:Genetic Variation; D006801:Humans; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology*
D017931:DNA Primers; C064269:FOSB protein, human; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1