SPARCL1 impedes trophoblast migration and invasion by down-regulating ERK phosphorylation and AP-1 production and altering EMT-related molecule expression

SPARCL1 通过下调 ERK 磷酸化和 AP-1 产生以及改变 EMT 相关分子表达来阻碍滋养层细胞迁移和侵袭

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作者:Xiaojing Liu, Jun Zhao, Xiaorui Luan, Shang Li, Junyu Zhai, Jiansheng Liu, Yanzhi Du

Conclusion

Restrained migration and invasion were noted in trophoblast cells with SPARCL1 overexpression, which might affect embryo implantation and placenta development. It could be involved in the pathogenesis of spontaneous abortion.

Methods

Villous specimens were obtained from 31 women with spontaneous abortion and 31 women with normal early pregnancy to determine the expression of SPARCL1. HTR8/SVneo cells and JAR cells were transfected with pIRES2-EGFP-SPARCL1 vectors and control vectors. The proliferation assay and scratch-wound assay were performed. Quantitative polymerase chain reaction (qPCR) and western blotting were performed to assess epithelial mesenchymal transition (EMT)-related molecules including MMP2, MMP3, N-cadherin, E-cadherin and vimentin. Extracellular signal-regulated kinase (ERK) phosphorylation activity and AP-1 expression in HTR8/SVneo cells following multi-scratching were detected using above assays.

Results

The mRNA and protein levels of SPARCL1 were significantly higher in the abortion group than in the normal pregnancy group. After transfection, there was no difference of cell viability between the SPARCL1-overexpression group and control vector group. However, the migration distance and area were reduced and the abundances of EMT related molecules were changed by SPARCL1 overexpression when compared with controls. Lower ERK phosphorylation activity and decreased Fos and Jun expressions were noted at high level of SPARCL1.

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