title: Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion.
abstract: OBJECTIVE
  We investigated the norepinephrine transporter (NET) expression in normal and pre-eclamptic placentas and analyzed the invasion activity of trophoblastic cells based on norepinephrine (NE)-NET regulation.
  
  
  METHODS
  NET and NE expression levels were examined by western blot and enzyme-linked immunosorbent assay, respectively. Trophoblast invasion activity, depending on NE-NET regulation, was determined by NET-small interfering RNA (siRNA) and NET transfection into the human extravillous trophoblast cells with or without NE treatment and invasion rates were analyzed by zymography and an invasion assay.
  
  
  RESULTS
  NET mRNA was expressed at a low level in pre-eclamptic placentas compared with normal placentas and NE concentration in maternal plasma increased significantly in pre-eclamptic women compared to normal pregnant women (p<0.05). NET gene upregulation and NE treatment stimulated trophoblast cell invasion up to 2.5-fold (p<0.05) by stimulating matrix metalloproteinase-9 activity via the phosphoinositol-3-kinase/AKT signaling pathway, whereas NET-siRNA with NE treatment reduced invasion rates.
  
  
  CONCLUSIONS
  NET expression is reduced by inadequate regulation of NE levels during placental development. This suggests that a complementary balance between NET and NE regulates trophoblast cell invasion activities during placental development.
authors.affiliation: Department of Biomedical Science, CHA University, Seoul, Korea.
authors.forename: Kyu-Hwan
authors.initials: KH
authors.lastname: Na
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Chun-Hyung
authors.initials: CH
authors.lastname: Kim
authors.forename: Kwang-Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Gi Jin
authors.initials: GJ
authors.lastname: Kim
keywords: Enzyme-linked immunosorbent assay; Norepinephrine transporter; Placenta; Pre-eclampsia; Small interfering RNA