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EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2.
- Source :
-
Acta medica Okayama [Acta Med Okayama] 2021 Dec; Vol. 75 (6), pp. 677-684. - Publication Year :
- 2021
-
Abstract
- Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy.<br />Competing Interests: No potential conflict of interest relevant to this article was reported.
- Subjects :
- Cell Line
Female
Humans
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Placenta metabolism
Pregnancy
Receptors, G-Protein-Coupled
Receptors, Peptide metabolism
Signal Transduction
Up-Regulation
Uterine Artery
Trophoblasts metabolism
Vascular Endothelial Growth Factor, Endocrine-Gland-Derived metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0386-300X
- Volume :
- 75
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Acta medica Okayama
- Publication Type :
- Academic Journal
- Accession number :
- 34955534
- Full Text :
- https://doi.org/10.18926/AMO/62806