Evidence-Based View of Safety and Effectiveness of Prokineticin Receptors Antagonists during Pregnancy.
EG-VEGF
angiogenesis
pregnancy pathologies
prokineticin antagonists
therapy
trophoblast invasion
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
17 Mar 2021
17 Mar 2021
Historique:
received:
31
01
2021
revised:
04
03
2021
accepted:
13
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
4
4
2021
Statut:
epublish
Résumé
Endocrine gland derived vascular endothelial growth factor (EG-VEGF) is a canonical member of the prokineticin (PROKs) family. It acts via the two G-protein coupled receptors, namely PROKR1 and PROKR2. We have recently demonstrated that EG-VEGF is highly expressed in the human placenta; contributes to placental vascularization and growth and that its aberrant expression is associated with pregnancy pathologies including preeclampsia and fetal growth restriction. These findings strongly suggested that antagonization of its receptors may constitute a potential therapy for the pregnancy pathologies. Two specific antagonists of PROKR1 (PC7) and for PROKR2 (PKRA) were reported to reverse PROKs adverse effects in other systems. In the view of using these antagonists to treat pregnancy pathologies, a proof of concept study was designed to determine the biological significances of PC7 and PKRA in normal pregnancy outcome. PC7 and PKRA were tested independently or in combination in trophoblast cells and during early gestation in the gravid mouse. Both independent and combined treatments uncovered endogenous functions of EG-VEGF. The independent use of antagonists distinctively identified PROKR1 and PROKR2-mediated EG-VEGF signaling on trophoblast differentiation and invasion; thereby enhancing feto-placental growth and pregnancy outcome. Thus, our study provides evidence for the potential safe use of PC7 or PKRA to improve pregnancy outcome.
Identifiants
pubmed: 33802771
pii: biomedicines9030309
doi: 10.3390/biomedicines9030309
pmc: PMC8002561
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Fondation pour la Recherche Médicale
ID : SPF20150934074
Organisme : VALO-GRAL CBH-EUR-GS (ANR-17-EURE-0003)
ID : VALO-GRAL CBH-EUR-GS (ANR-17-EURE-0003)
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