G protein-coupled estrogen receptor stimulates human trophoblast cell invasion via YAP-mediated ANGPTL4 expression.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
12 11 2021
12 11 2021
Historique:
received:
31
05
2021
accepted:
25
10
2021
entrez:
13
11
2021
pubmed:
14
11
2021
medline:
21
12
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34773076
doi: 10.1038/s42003-021-02816-5
pii: 10.1038/s42003-021-02816-5
pmc: PMC8589964
doi:
Substances chimiques
ANGPTL1 protein, human
0
Angiopoietin-Like Protein 1
0
Cell Cycle Proteins
0
GPER1 protein, human
0
Receptors, Estrogen
0
Receptors, G-Protein-Coupled
0
Transcription Factors
0
YY1AP1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1285Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32050410302
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32070848
Informations de copyright
© 2021. The Author(s).
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