GNA11 differentially mediates fibroblast growth factor 2-and vascular endothelial growth factor A-induced cellular responses in human fetoplacental endothelial cells

During pregnancy, fetoplacental angiogenesis is dramatically increased in association with rapidly elevated blood flow. Any disruption of fetoplacental angiogenesis may lead to pregnancy complications such as intrauterine growth restriction. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are crucial regulators of fetoplacental angiogenesis. G protein alpha subunits q (GNAq) and 11 (GNA11) are two members of the G alpha(q/11) subfamily involved in mediating vascular growth and basal blood pressure. However, little is known about the roles of GNA11 alone with respect to mediating the FGF2- and VEGFA-induced fetoplacental endothelial function. Using a cell model of human umbilical cord vein endothelial cells cultured under physiological chronic low O-2 (3% O-2), we showed that GNA11 small interfering RNA (siRNA) dramatically inhibited (P<0.05) FGF2- and VEGFA-stimulated fetoplacental endothelial migration (by similar to 36% and similar to 50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated (P<0.05) FGF2- and VEGFA-induced phosphorylation of phospholipase C-beta 3 (PLC beta 3) at S537 in a time-dependent fashion but not mitogen-activated protein kinase 3/1 (ERK1/2) and v-akt murine thymoma viral oncogene homologue 1 (AKT1). These data suggest that GNA11 mediates FGF2- and VEGFA-stimulated fetoplacental endothelial cell migration partially via altering the activation of PLC beta 3.