Decreased Filamin b expression regulates trophoblastic cells invasion through ERK/MMP-9 pathway in pre-eclampsia.

OBJECTIVES: The purpose of this study was to investigate the expression of Filamin b in the placental placenta of patients with early or late onset pre-eclampsia (PE) and its potential effects on the pathophysiology of the disease. METHODS AND METHODS: Immunohistochemistry staining, western blot assays and real time PCR were used to detect the expression level of FLN-b. The expression levels of MMP-2, MMP-9 and ERK1/2 proteins from control and FLN-b-silenced JEG-3 cells were also detected by western blot and JEG-3 cell invasion. RESULTS: Compared with normal term pregnancies placentas, the FLN-b expression was significantly lower than that of women with PE, its level in late-onset PE is lower than in early-onset PE. In FLN-b-silenced JEG-3 cells, the protein levels of MMP-2, MMP-9 and phosphorylated ERK1/2 decreased markedly and the number of cells penetrating through the transwell chamber membrane is also greatly reduced. CONCLUSIONS: Down-regulation of FLN-b inhibits the ERK/MMP-2 and MMP-9 pathways, leading to trophoblastic invasion disorders in the PE placenta.

Increased NDRG1 expression attenuate trophoblast invasion through ERK/MMP-9 pathway in preeclampsia.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Upregulation of NDRG1 is associated with impaired trophoblast invasion in PE by inhibition ERK/MMP-2 and MMP-9 Pathway.