CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Novel participation of the Multidrug Resistance-Associated Protein 4 (MRP4) transporter in LPA1-mediated HTR-8/SVneo cell migration.
Autor/es:
SORDELLI, MS; DAVIO, CARLOS; BELTRAME, JS; RIBEIRO, ML; CAÑUMIL, VA
Lugar:
París
Reunión:
Congreso; Society for Reproductive Investigation; 2019
Institución organizadora:
Society for Reproductive Investigation
Resumen:
Introduction: An intricate molecular dialogue between trophoblastand uterus initiates the process of implantation. After the embryo attaches tothe lining of the uterus, trophoblast cells begin a proliferative, migratingand invasive process infiltrating the decidua and remodeling uterinevasculature. Novel insights about the role played by lipids in theestablishment of early pregnancy have sparked a renewed interest inunderstanding them as reproductive bioactive molecules. In this sense, lysophosphatidicacid (LPA) and prostaglandin E2 (PGE2) are well-known mediators of embryoimplantation. LPA has pleiotropic functions by binding to six G-protein coupledreceptors. Besides, PGE2 exerts a pivotal participation in decidualization andvascular remodeling. In the last years, MRP4 transporter has been described asan additional checkpoint that regulates PGE2 efflux.Trophoblast migration is accomplished by molecular andcellular interactions controlled by the maternal-fetal interface microenvironment.Defects in this mechanism might contribute to certain obstetric complications. Wehave previously reported that LPA augments trophoblast cell migration and stimulatesPGE2 production. Therefore, we aimed to investigate the interaction between LPAand MRP4 in human first trimester trophoblast cell migration. Methods: HTR-8/SVneo cell line (H8) was used as a model of human first trimester extravillous trophoblast. A pharmacologicalin vitro strategy was designed. H8cells were incubated with LPA 5x10-5M, LPA+BMT (10-5M, anLPA1 antagonist), LPA+AH6809 (10-6M, an EP1/EP2 antagonist), LPA+AH 23848(10-6M, an EP4 antagonist) or LPA+MK-571 (10-5M, an MRP4inhibitor). LPA concentration was selected based on the physiologicalconcentration found in plasma of women in the first trimester of gestation. Cellswere subjected to migration (wound healing assay, 18h). MRP4 expression wascharacterized by PCR and western blot.Results: LPA+BMTcompletely reversed LPA effect on trophoblast migration (p