G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression.

Autor: Cheng JC; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China. jungchien.cheng@gmail.com., Fang L; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Li Y; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Thakur A; Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada, V5Z 1L3.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada, V6T 1Z4., Hoodless PA; Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada, V5Z 1L3.; Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada, V6T 1Z4.; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada, V6T 1Z4., Guo Y; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Wang Z; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Wu Z; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Yan Y; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Jia Q; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Gao Y; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Han X; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Yu Y; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China., Sun YP; Center for Reproductive Medicine, Henan Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, China. syp2008@vip.sina.com.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Nov 12; Vol. 4 (1), pp. 1285. Date of Electronic Publication: 2021 Nov 12.
DOI: 10.1038/s42003-021-02816-5
Abstrakt: Insufficient invasion of trophoblast cells into the uterine decidua is associated with preeclampsia (PE). G protein-coupled estrogen receptor (GPER) is a membrane estrogen receptor involved in non-genomic estrogen signaling. GPER is expressed in human trophoblast cells and downregulated GPER levels are noted in PE. However, to date, the role of GPER in trophoblast cells remains largely unknown. Here, we applied RNA sequencing (RNA-seq) to HTR-8/SVneo human trophoblast cells in response to G1, an agonist of GPER, and identified angiopoietin-like 4 (ANGPTL4) as a target gene of GPER. Treatment of trophoblast cells with G1 or 17β-estradiol (E2) activated Yes-associated protein (YAP), the major downstream effector of the Hippo pathway, via GPER but in a mammalian STE20-like protein kinase 1 (MST1)-independent manner. Using pharmacological inhibitors as well as loss- and gain-of-function approaches, our results revealed that YAP activation was required for GPER-stimulated ANGPTL4 expression. Transwell invasion assays demonstrated that activation of GPER-induced ANGPTL4 promoted cell invasion. In addition, the expression levels of GPER, YAP, and ANGPTL4 were downregulated in the placenta of patients with PE. Our findings reveal a mechanism by which GPER exerts its stimulatory effect on human trophoblast cell invasion by upregulating YAP-mediated ANGPTL4 expression.
(© 2021. The Author(s).)
Databáze: MEDLINE
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