title: Response gene to complement 32 deficiency causes impaired placental angiogenesis in mice.
abstract: OBJECTIVE
  The objectives of this study are to determine the role of response gene to complement 32 (RGC-32) in the placental angiogenesis during pregnancy and explore the underlying mechanisms.
  
  
  RESULTS
  RGC-32-deficient (RGC32(-/-)) mice were generated from C57BL/6 embryonic stem cells with deletion of exon 2 and 3 of the RGC-32 gene. Most of the RGC32(-/-) mice can survive. However, their body sizes were much smaller compared with their wild-type littermates when they were born. By examining the embryo development and placentas at 16.5 days post-coitum, we found that RGC32(-/-) embryos and foetal placentas were significantly smaller than the wild-type. Further analysis showed that the labyrinth zone of RGC32(-/-) placenta was smaller with defective angiogenesis. Mechanistically, vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and placental growth factor (PlGF) were significantly down-regulated in RGC32(-/-) placentas, suggesting that VEGFR2 and PlGF may mediate RGC-32 function in placental angiogenesis. Indeed, knockdown of RGC-32 by shRNA inhibited VEGF-induced endothelial cell proliferation, migration, and tube formation while blocking VEGFR2 expression. RGC-32 appeared to regulate VEGFR2 expression via activation of NF-kB. Moreover, RGC-32 regulated trophoblasts proliferation via control of PlGF expression.
  
  
  CONCLUSIONS
  Absence of RGC-32 caused foetal growth restriction through interrupting the placental angiogenesis, which was due to the decrease in VEGFR2 expression through the NF-kB-dependent pathway in endothelial cells and PlGF expression in trophoblasts.
authors.affiliation: Department of Physiology and Pharmacology, University of Georgia, Athens, 30602, USA.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cui
authors.forename: Xia
authors.initials: X
authors.lastname: Guo
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005260:Female; D047109:Fetal Development; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000502:physiology; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000502:physiology; D014327:Trophoblasts / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology
chemical_list: D016328:NF-kappa B; D009687:Nuclear Proteins; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; C520017:Rgc-32 protein, mouse; D000072483:Placenta Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Foetal growth restriction; Placental growth factor; Response gene to complement 32; Vascular endothelial growth factor receptor