Fu Yufen, Wei Jufeng, Dai Xueli, Ye Yuanhua
Department of Obstetrics and Gynecology, Qingdao University, Qingdao 266000, China; Department of Obstetrics, Zibo Maternity and Child Health Hospital, Zibo 255000, China.
Department of Obstetrics and Gynecology, Qingdao University, Qingdao 266000, China; Department of Obstetrics, Qingdao Central Hospital, Qingdao 266000, China.
Placenta. 2017 Mar;51:76-81. doi: 10.1016/j.placenta.2017.01.126. Epub 2017 Feb 3.
The aim of this study was to investigate the expression of N-myc downstream-regulated gene1(NDRG1)in the placentas of pregnancies complicated with early-onset and late-onset preeclampsia (PE) and its underlying mechanism on the pathophysiology of PE.
The expressions of NDRG-1 in placentas of pregnancies complicated with early-onset PE and late-onset PE were detected using immunohistochemistry, western blot assays and fluorescence quantitative PCR. The expressions of MMP-2, MMP-9 and ERK1/2 protein were detected by western blot analysis and cell invasion assay was performed using transwell chambers in NDRG1 silenced JEG-3 cells.
Compared with the normal term pregnancies, the expression of both NDRG1 mRNA and protein were significantly high in placentas from PE, and the expression of NDRG1 in early-onset PE was higher than that in late-onset PE. In NDRG1-silenced JEG-3 cells, MMP-2, MMP-9 and phosphorylation of ERK1/2 protein increased obviously and the number of cells that penetrated the membrane increased.
Upregulation of NDRG1 is associated with impaired trophoblast invasion in PE by inhibition ERK/MMP-2 and MMP-9 Pathway.
本研究旨在探讨N - myc下游调控基因1（NDRG1）在早发型和晚发型子痫前期（PE）孕妇胎盘组织中的表达情况及其在PE病理生理过程中的潜在机制。
采用免疫组织化学、蛋白质印迹法及荧光定量PCR检测早发型PE和晚发型PE孕妇胎盘组织中NDRG - 1的表达。通过蛋白质印迹分析检测MMP - 2、MMP - 9及ERK1/2蛋白的表达，并在NDRG1沉默的JEG - 3细胞中使用Transwell小室进行细胞侵袭实验。
与足月正常妊娠相比，PE患者胎盘组织中NDRG1 mRNA和蛋白的表达均显著升高，且早发型PE中NDRG1表达高于晚发型PE。在NDRG1沉默的JEG - 3细胞中，MMP - 2、MMP - 9及ERK1/2蛋白磷酸化水平明显升高且穿膜细胞数量增加。
NDRG1上调与PE中滋养细胞侵袭受损有关，其机制可能是通过抑制ERK/MMP - 2和MMP - 9通路实现的。
