Amphiregulin promotes trophoblast invasion and increases MMP9/TIMP1 ratio through ERK1/2 and Akt signal pathways

被引:22
作者
Yu, Yiping [1 ,2 ]
Fang, Lanlan [1 ,2 ]
Wang, Sijia [1 ,2 ]
Li, Yiran [1 ,2 ]
Guo, Yanjie [1 ,2 ]
Sun, Ying-pu [1 ,2 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Reprod Med Ctr, Zhengzhou 450052, Henan, Peoples R China
[2] Henan Prov Key Lab Reprod & Genet, Zhengzhou 450052, Henan, Peoples R China
基金
中国国家自然科学基金;
关键词
Amphiregulin; HTR-8/SVneo cell; MMP9/TIMP-1; ratio; Invasiveness; ERK1/2; Akt; EPIDERMAL-GROWTH-FACTOR; TISSUE INHIBITORS; MATRIX METALLOPROTEINASES; HUMAN PLACENTA; CELL-LINE; EXPRESSION; ACTIVATION; MIGRATION; DECIDUA; ROLES;
D O I
10.1016/j.lfs.2019.116899
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Aims: The aim of our study is to illustrate the role of amphiregulin in trophoblast invasiveness and underlying signal cascades. Main methods: An immortalized human early extravillous cell line, HTR-8/SVneo, was used for this investigation. Matrigel-transwell invasion assay was used for testing the effects of amphiregulin on cell invasiveness. MMP9 and MMP2 mRNA expression level and activity were measured using Rt-qPCR and zymographic analysis. Cell signals involved in the invasion process were verified using western blot and specific inhibitors. Key findings: Our results showed that amphiregulin could promote HTR-8/SVneo cell invasiveness without interfering cell proliferation, and significantly upregulate the expression of MMP9 and TIMP-1 mRNAs as well as the ratio of MMP9/TIMP-1. Using specific inhibitors for MEK and PI3K signaling further indicated that, both ERK1/2 and Akt signal pathways were required for amphiregulin-induced cell invasiveness. The co-ordination between ERK1/2 and Akt signaling pathway was needed for the upregulation of MMP9 mRNA, while ERK1/2 was more essential for the upregulation of TIMP-1 mRNA. Meanwhile, we first put forward that the deficiency of amphiregulin expression in trophoblast might be compensated by the upregulation of epidermal growth factor receptor (EGFR) and heparin-binding EGF (HB-EGF) mRNA. Significance: ERK1/2 and Akt signaling pathways mediate amphiregulin-induced upregulation of MMP9 mRNA and the MMP9/TIMP-1 ratio, which subsequently contribute to amphiregulin-promotion of HTR-8/SVneo cell invasion.
引用
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页数:11
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