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.
OBJECTIVE
To 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.


METHODS
Experimental laboratory study.


METHODS
University gynecology unit.


METHODS
Infertile women undergoing diagnostic laparoscopy for assessment of tubal patency.


METHODS
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.


METHODS
Cell proliferation, tube formation, and molecules of cell-signaling pathways in the treated UtMVEC-Myo.


RESULTS
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.


CONCLUSIONS
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.
Department of Obstetrics and Gynaecology, University of Hong Kong, Pokfulam, Hong Kong, Republic of China.
Yin-Lau
YL
Lee
Yuk-Ling
YL
Chan
Wan-Ngai
WN
Chow
Ernest Hung-Yu
EH
Ng
Kai-Fai
KF
Lee
William S B
WS
Yeung
Pak-Chung
PC
Ho
D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects*; D004702:Endocrine Glands / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006801:Humans; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014599:Uterus / Q000098:blood supply*; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived / Q000494:pharmacology / Q000502:physiology*
D012333:RNA, Messenger; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases