Altered expression of norepinephrine transporter and norepinephrine in human placenta cause pre-eclampsia through regulated trophoblast invasion.
10.5653/cerm.2013.40.1.12
- Author:
Kyu Hwan NA
1
;
Jong Ho CHOI
;
Chun Hyung KIM
;
Kwang Soo KIM
;
Gi Jin KIM
Author Information
1. Department of Biomedical Science, CHA University, Seoul, Korea. gjkim@cha.ac.kr
- Publication Type:Original Article
- Keywords:
Placenta;
Pre-eclampsia;
Norepinephrine transporter;
Enzyme-linked immunosorbent assay;
Small interfering RNA
- MeSH:
Blotting, Western;
Enzyme-Linked Immunosorbent Assay;
Female;
Humans;
Matrix Metalloproteinase 9;
Norepinephrine;
Norepinephrine Plasma Membrane Transport Proteins;
Placenta;
Placentation;
Plasma;
Pre-Eclampsia;
Pregnant Women;
RNA;
RNA, Messenger;
RNA, Small Interfering;
Transfection;
Trophoblasts;
Up-Regulation
- From:Clinical and Experimental Reproductive Medicine
2013;40(1):12-22
- CountryRepublic of Korea
- Language:English
-
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. 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.
