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The 5-HT2A serotonin receptor enhances cell viability, affects cell cycle progression and activates MEK-ERK1/2 and JAK2-STAT3 signalling pathways in human choriocarcinoma cell lines

Oufkir, Talal; Arseneault, Madeleine; Sanderson, J. Thomas ORCID logoORCID: https://orcid.org/0000-0002-3190-2811 et Vaillancourt, Cathy ORCID logoORCID: https://orcid.org/0000-0003-0543-6244 (2010). The 5-HT2A serotonin receptor enhances cell viability, affects cell cycle progression and activates MEK-ERK1/2 and JAK2-STAT3 signalling pathways in human choriocarcinoma cell lines Placenta , vol. 31 , nº 5. pp. 439-447. DOI: 10.1016/j.placenta.2010.02.019.

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Résumé


Previous results from our group have demonstrated the expression of the 5-HT2A receptor and a mitogenic effect of serotonin in human trophoblast. The objectives of the present study were to investigate the role of the 5-HT2A receptor in trophoblast cells and to determine the signalling pathways activated by this receptor. We investigated the effect of (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI), a selective 5-HT2A agonist, on cell cycle progression and cell viability in BeWo and JEG-3 cells. We also investigated, by co-immunoprecipitation and western blot analysis, the involvement of the MEK-ERK1/2 and JAK2-STAT3 signalling pathways following activation of the placental 5-HT2A receptor. Our results showed a concentration-dependent increase of cell viability by DOI, which was reversed by ketanserin, a selective 5-HT2A receptor antagonist. Furthermore, activation of the 5-HT2A receptor by DOI increased cell entry into the G2/M and S phase (DNA synthesis) in BeWo and JEG-3 cells, respectively. In addition, stimulation of BeWo and JEG-3 cells by DOI activated both the MEK-ERK1/2 and the JAK2-STAT3 signalling pathways. This study demonstrated that the 5-HT2A receptor increases cell viability and affects cell cycle progression in human trophoblast cell lines as well as activates the MEK-ERK1/2 and JAK2-STAT3 intracellular signalling pathways, which are related to survival, differentiation, migration and invasion. These findings indicate that serotonin through the activation of the 5-HT2A receptor is a key regulator of placentation and may play a role in the pathophysiology of certain pregnancy disorders associated with alterations in placental development, such as preeclampsia, gestational diabetes and preterm birth.

Type de document: Article
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 07 juill. 2025 18:44
Dernière modification: 07 juill. 2025 18:44
URI: https://espace.inrs.ca/id/eprint/15010

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