Induction of trophoblast cell fusion by a protein tyrosine phosphatase inhibitor.
In the placenta, trophoblast cell fusion leads to the formation of the syncytiotrophoblast, which plays an essential role in the diffusion of nutrients and hormones from the mother to the fetus. Different protein tyrosine kinases are involved in the modulation of this biological process. Herein, we investigated the impact of a protein tyrosine phosphatase (PTP) inhibitor (bpV[pic]) on trophoblast fusion. Upon bpV[pic] or forskolin treatment, primary and BeWo trophoblastic cells demonstrated higher cAMP levels and a more potent induction of cell fusion, while non-fusogenic JEG-3 cells were non-responsive to these treatments. RT-PCR analyses on stimulated BeWo cells or primary cytotrophoblast cells demonstrated an increase in syncytin-1 mRNA levels, which was more pronounced upon forskolin/bpV[pic] treatment. Using the luciferase gene upstream of the syncytin-1 promoter, similar results were obtained in BeWo cells after stimulation. These results demonstrate that PTPs act negatively on cell fusion in human trophoblasts and could control the timing of syncytiotrophoblast formation during placenta development.
Vargas
A
A
Département des Sciences Biologiques and BioMed Research Center, Université du Québec à Montréal, 2080 St-Urbain, Montréal, QC, H2X 3X8, Canada.
Moreau
J
J
Le Bellego
F
F
Lafond
J
J
Barbeau
B
B
D002459:Cell Fusion; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015686:Gene Products, env / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009942:Organometallic Compounds / Q000494:pharmacology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000502:physiology; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection; D014327:Trophoblasts / Q000187:drug effects* / Q000502:physiology*
D004791:Enzyme Inhibitors; D015686:Gene Products, env; D009942:Organometallic Compounds; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; C119540:oxodiperoxo(pyridine-2-carboxylate)vanadate(V); C405335:syncytin; D008156:Luciferases; D017027:Protein Tyrosine Phosphatases