Endocrine gland–derived vascular endothelial growth factor stimulates proliferation and tube formation in human uterine microvascular endothelial cell through the mitogen-activated protein kinase but not through the Akt pathway

ObjectiveTo study the angiogenic functions of endocrine gland–derived vascular endothelial growth factor (EG-VEGF) on a normal myometrial uterine microvascular endothelial cell line (UtMVEC-Myo) and the signaling pathways elicited by EG-VEGF in UtMVEC-Myo.DesignExperimental laboratory study.SettingUniversity gynecology unit.Patient(s)Infertile women undergoing diagnostic laparoscopy for assessment of tubal patency.Intervention(s)Real-time polymerase chain reaction (PCR) analysis of mRNA of EG-VEGF and its receptors, PKR1 and PKR2, in UtMVEC-Myo and endometrial samples. The effects of EG-VEGF on the cell proliferation, tube formation, and cell signaling pathways of UtMVEC-Myo were studied.Main Outcome Measure(s)Cell proliferation, tube formation, and molecules of cell-signaling pathways in the treated UtMVEC-Myo.Result(s)UtMVEC-Myo cells had PKR1 and PKR2 but not EG-VEGF mRNA. EG-VEGF significantly stimulated cell proliferation and tube formation in UtMVEC-Myo cells. EG-VEGF activated p44/42 mitogen-activated protein kinase (MAPK) but not Akt signaling pathway. The effects of EG-VEGF on p44/42 MAPK phosphorylation and cell proliferation were nullified by the specific MAPK inhibitor, PD98059.Conclusion(s)EG-VEGF has a direct angiogenic effect on UtMVEC-Myo that expresses EG-VEGF receptors (PKR1 and PKR2) and modulates cell proliferation and sprouting of the endothelial cells. It is suggested that EG-VEGF enhanced cell proliferation through the activation of MAPK pathway but not through the Akt pathway.