title: Inhibition of Wnt Inhibitory Factor 1 Under Hypoxic Condition in Human Umbilical Vein Endothelial Cells Promoted Angiogenesis in Vitro.
abstract: Placentation is a complicated process critical for maternal-fetal exchange of nutrients and gases that includes stepwise vasculogenesis and angiogenesis. Wnt inhibitory factor 1 (WIF1) is a secreted Wnt antagonist that acts as a tumor-suppressor gene by antagonizing angiogenesis and proliferation and inducing apoptosis. The purpose of this study was to investigate the function of WIF1 on placental angiogenesis in human umbilical vein endothelial cells (HUVECs) under hypoxic conditions. We found that WIF1 was diversely expressed in placental vascular endothelial cells at different points during gestation and was weaker in the early placenta than in the term placenta. We validated the antiangiogenesis role of WIF1 by inhibiting proliferation, tube formation and migration, and inducing apoptosis of endothelial cells through antagonizing Wnt/β-catenin signaling pathway. We also identified that hypoxic conditions similar to the early placenta inhibited the expression of WIF1 and reversed the antiangiogenesis of WIF1 in HUVECs. In conclusion, our present study supported the hypothesis that WIF1 is crucial as a negative regulator of the functions of endothelial cells in angiogenesis and that hypoxia plays an important role in controlling WIF1 expression and angiogenesis. We also demonstrated that Wnt/β-catenin signaling pathway was activated in correspondence with the suppression of WIF1 in the angiogenesis of endothelial cells under hypoxic conditions.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and family planning Science and Technology Research Institute, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Qinyin
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shan
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Baker
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tong
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Canada-China-New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, China qihongbocy@gmail.com.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Qi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D003656:Decidua / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D012097:Repressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C485569:WIF1 protein, human; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein
keywords: Wnt inhibitory factor 1; angiogenesis; human umbilical vein endothelial cells; hypoxia