P-Glycoprotein (P-gp)/ABCB1 plays a functional role in extravillous trophoblast (EVT) invasion and is decreased in the pre-eclamptic placenta.

Autor: Dunk CE; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Pappas JJ; Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.; Department of Physiology, University of Toronto, Toronto, Canada., Lye P; Department of Physiology, University of Toronto, Toronto, Canada., Kibschull M; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Javam M; Department of Physiology, University of Toronto, Toronto, Canada., Bloise E; Department of Physiology, University of Toronto, Toronto, Canada.; Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil., Lye SJ; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Physiology, University of Toronto, Toronto, Canada.; Departments of Obstetrics and Gynecology and Medicine, University of Toronto, Toronto, Canada., Szyf M; Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada., Matthews SG; Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Physiology, University of Toronto, Toronto, Canada.; Departments of Obstetrics and Gynecology and Medicine, University of Toronto, Toronto, Canada.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2018 Nov; Vol. 22 (11), pp. 5378-5393. Date of Electronic Publication: 2018 Sep 05.
DOI: 10.1111/jcmm.13810
Abstrakt: 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/SV neo 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.
(© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)
Databáze: MEDLINE
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