INVESTIGADORES
VOTA daiana Marina
congresos y reuniones científicas
Título:
INTERPLAY BETWEEN VIP AND mTOR IN TROPHOBLAST CELL NUTRIENT UPTAKE. IMPACT ON THE TROPHOBLAST-IMMUNE INTERACTION
Autor/es:
F MERECH; D PAPARINI; V HAUK; E SOCZEWSKI; R RAMHORST; C PEREZ LEIRSÓS; D. VOTA
Reunión:
Congreso; Reunion Anual de la Sociedad de Investigaciones Clínicas; 2019
Resumen:
The transport of nutrients by cytotrophoblast cells regulates placental metabolism throughout pregnancy. The mammalian target of Rapamycin (mTOR) functions as a placental growth signaling sensor and modulates nutrient transporters expressed on trophoblast cells (Tb). A decreased placental mTOR activity was reported in pregnancies complicated by placental insufficiency and intrauterine growth restriction. We have previously shown that the vasoactive intestinal peptide (VIP) stimulates human cytotrophoblast cell glucose and amino acid uptake along with increased GLUT1/3 and SNAT1 expression. Accordingly, a murine pregnancy model with VIP-deficient Tb cells presented reduced fetal weight at day 14.5. Here we deepened into the mechanisms of nutrient transport induced by VIP in cytotrophoblast cells focusing on the interplay between exogenous/endogenous VIP and mTOR activity. Also, based on the close regulatory interaction of cytotrophoblast cells and maternal leukocytes at the early maternal-placental interface, we explored glucose uptake by monocytes conditioned by VIP and Tb cell factors. The human Tb cell lines Swan-71/BeWo were used. VIP knocking-down was carried out with a VIP siRNA. System A activity was measured by 14C-MeAIB incorporation and VIP/mTOR expression by qRT-PCR and flow cytometry. mTOR phosphorylation was studied by western blotting. Glucose uptake in CD14+ monocytes isolated from peripheral blood was assessed by flow cytometry using the fluorescent analog 2-NBDG. VIP stimulated Na+-dependent 14C-MeAIB uptake in Tb cells (n=4; p