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.
Lee
Yin-Lau
YL
Department of Obstetrics and Gynaecology, University of Hong Kong, Pokfulam, Hong Kong, Republic of China.
Chan
Yuk-Ling
YL
Chow
Wan-Ngai
WN
Ng
Ernest Hung-Yu
EH
Lee
Kai-Fai
KF
Yeung
William S B
WS
Ho
Pak-Chung
PC
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