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GNA11 differentially mediates fibroblast growth factor 2‐ and vascular endothelial growth factor A‐induced cellular responses in human fetoplacental endothelial cells
Author(s) -
Zou Qingyun,
Zhao Yingjie,
Li Hua,
Wang Xiangzhen,
Liu Aixia,
Zhong Xinqi,
Yan Qin,
Li Yan,
Zhou Chi,
Zheng Jing
Publication year - 2018
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp275677
Subject(s) - angiogenesis , vascular endothelial growth factor a , vascular endothelial growth factor b , biology , medicine , endocrinology , microbiology and biotechnology , vascular endothelial growth factor , vascular endothelial growth factor c , fibroblast growth factor , cancer research , receptor , vegf receptors
Key points Fetoplacental vascular growth is critical to fetal growth. Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor A (VEGFA) are two major regulators of fetoplacental vascular growth. G protein α subunit 11 (GNA11) transmits signals from many external stimuli to the cellular interior and may mediate endothelial function. It is not known whether GNA11 mediates FGF2‐ and VEGFA‐induced endothelial cell responses under physiological chronic low O 2 . In the present study, we show that knockdown of GNA11 significantly decreases FGF2‐ and VEGFA‐induced fetoplacental endothelial cell migration but not proliferation and permeability. Such decreases in endothelial migration are associated with increased phosphorylation of phospholipase C‐β3. The results of the present study suggest differential roles of GNA11 with respect to mediating FGF2‐ and VEGFA‐induced fetoplacental endothelial function.Abstract 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 α subunits q (GNAq) and 11 (GNA11) are two members of the Gα 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 ∼36% and ∼50%, respectively) but not proliferation and permeability. GNA11 siRNA also elevated ( P < 0.05) FGF2‐ and VEGFA‐induced phosphorylation of phospholipase C‐β3 (PLCβ3) 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 PLCβ3.