Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells

The transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here w...

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Autores principales: Merech, Fatima, Soczewski, Elizabeth, Hauk, Vanesa, Paparini, Daniel, Ramhorst, Rosanna, Vota, Daiana, Pérez Leirós, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868285/
https://www.ncbi.nlm.nih.gov/pubmed/31748639
http://dx.doi.org/10.1038/s41598-019-53676-3
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author Merech, Fatima
Soczewski, Elizabeth
Hauk, Vanesa
Paparini, Daniel
Ramhorst, Rosanna
Vota, Daiana
Pérez Leirós, Claudia
author_facet Merech, Fatima
Soczewski, Elizabeth
Hauk, Vanesa
Paparini, Daniel
Ramhorst, Rosanna
Vota, Daiana
Pérez Leirós, Claudia
author_sort Merech, Fatima
collection PubMed
description The transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here we explored the effect of VIP on glucose and System A amino acid uptake by human trophoblast-derived cells (Swan 71 and BeWo cell lines). VIP activated D-glucose specific uptake in single cytotrophoblast cells in a concentration-dependent manner through PKA, MAPK, PI3K and mTOR signalling pathways. Glucose uptake was reduced in VIP-knocked down cytotrophoblast cells. Also, VIP stimulated System A amino acid uptake and the expression of GLUT1 glucose transporter and SNAT1 neutral amino acid transporter. VIP increased mTOR expression and mTOR/S6 phosphorylation whereas VIP silencing reduced mTOR mRNA and protein expression. Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Our findings support a role of VIP in the transport of glucose and neutral amino acids in cytotrophoblast cells through mTOR-regulated pathways and they are instrumental for understanding the physiological regulation of nutrient sensing by endogenous VIP at the maternal-foetal interface.
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spelling pubmed-68682852019-12-04 Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells Merech, Fatima Soczewski, Elizabeth Hauk, Vanesa Paparini, Daniel Ramhorst, Rosanna Vota, Daiana Pérez Leirós, Claudia Sci Rep Article The transport of nutrients across the placenta involves trophoblast cell specific transporters modulated through the mammalian target of rapamycin (mTOR). The vasoactive intestinal peptide (VIP) has embryotrophic effects in mice and regulates human cytotrophoblast cell migration and invasion. Here we explored the effect of VIP on glucose and System A amino acid uptake by human trophoblast-derived cells (Swan 71 and BeWo cell lines). VIP activated D-glucose specific uptake in single cytotrophoblast cells in a concentration-dependent manner through PKA, MAPK, PI3K and mTOR signalling pathways. Glucose uptake was reduced in VIP-knocked down cytotrophoblast cells. Also, VIP stimulated System A amino acid uptake and the expression of GLUT1 glucose transporter and SNAT1 neutral amino acid transporter. VIP increased mTOR expression and mTOR/S6 phosphorylation whereas VIP silencing reduced mTOR mRNA and protein expression. Inhibition of mTOR signalling with rapamycin reduced the expression of endogenous VIP and of VIP-induced S6 phosphorylation. Our findings support a role of VIP in the transport of glucose and neutral amino acids in cytotrophoblast cells through mTOR-regulated pathways and they are instrumental for understanding the physiological regulation of nutrient sensing by endogenous VIP at the maternal-foetal interface. Nature Publishing Group UK 2019-11-20 /pmc/articles/PMC6868285/ /pubmed/31748639 http://dx.doi.org/10.1038/s41598-019-53676-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Merech, Fatima
Soczewski, Elizabeth
Hauk, Vanesa
Paparini, Daniel
Ramhorst, Rosanna
Vota, Daiana
Pérez Leirós, Claudia
Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title_full Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title_fullStr Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title_full_unstemmed Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title_short Vasoactive Intestinal Peptide induces glucose and neutral amino acid uptake through mTOR signalling in human cytotrophoblast cells
title_sort vasoactive intestinal peptide induces glucose and neutral amino acid uptake through mtor signalling in human cytotrophoblast cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868285/
https://www.ncbi.nlm.nih.gov/pubmed/31748639
http://dx.doi.org/10.1038/s41598-019-53676-3
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