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, Δ FosB, 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.