Na, Kyu-HwanChoi, Jong HoKim, Chun-HyungKim, Kwang-SooKim, Gi Jin2013-10-312013Na, Kyu-Hwan, Jong Ho Choi, Chun-Hyung Kim, Kwang-Soo Kim, and Gi Jin Kim. 2013. Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion. Clinical and Experimental Reproductive Medicine 40(1): 12-22.2233-8233http://nrs.harvard.edu/urn-3:HUL.InstRepos:11238937Objective: 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. Conclusion: 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.en-USPlacentaPre-eclampsiaNorepinephrine transporterEnzyme-linked immunosorbent assaySmall interfering RNAJournal Article2013-10-3110.5653/cerm.2013.40.1.12