P-Glycoprotein (P-gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre-eclamptic placenta.
J Cell Mol Med
; 22(11): 5378-5393, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30256530
ABSTRACT
Dysregulation of trophoblast differentiation is implicated in the placental pathologies of intrauterine growth restriction and pre-eclampsia. P-glycoprotein (P-gp encoded by ABCB1) is an ATP-binding cassette transporter present in the syncytiotrophoblast layer of the placenta where it acts as a molecular sieve. In this study, we show that P-gp is also expressed in the proliferating cytotrophoblast (CT), the syncytiotrophoblast (ST) and the extravillous trophoblast (EVT), suggesting our hypothesis of a functional role for P-gp in placental development. Silencing of ABCB1, via siRNA duplex, results in dramatically reduced invasion and migration, and increased tube formation and fusion in the EVT-like HTR8/SVneo cell line. In both EVT and CT explant differentiation experiments, silencing of ABCB1 leads to induction of the fusion markers human hCG, ERVW-1 and GJA1 and terminal differentiation of both trophoblast subtypes. Moreover, P-gp protein levels are decreased in both the villous and the EVT of severe early-onset pre-eclamptic placentas. We conclude that, in addition to its role as a syncytial transporter, P-gp is a key factor in the maintenance of both CT and EVT lineages and that its decrease in severe pre-eclampsia may contribute to the syncytial and EVT placental pathologies associated with this disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Placentación
/
Preeclampsia
/
Trofoblastos
Límite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
J Cell Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Canadá