Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.

Vascular endothelial growth factor (VEGF) is up-regulated during mesothelial to mesenchymal transition (MMT) and has been associated with peritoneal membrane dysfunction in peritoneal dialysis (PD) patients. It has been shown that normal and malignant mesothelial cells (MCs) express VEGF receptors (...

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Autores principales:	María Luisa Pérez-Lozano, Pilar Sandoval, Angela Rynne-Vidal, Abelardo Aguilera, José Antonio Jiménez-Heffernan, Patricia Albar-Vizcaíno, Pedro L Majano, José Antonio Sánchez-Tomero, Rafael Selgas, Manuel López-Cabrera
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a2e5237e824946a891c52bbbd29b9112
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spelling	oai:doaj.org-article:a2e5237e824946a891c52bbbd29b91122021-11-18T07:50:06ZFunctional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.1932-620310.1371/journal.pone.0060776https://doaj.org/article/a2e5237e824946a891c52bbbd29b91122013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23585849/?tool=EBIhttps://doaj.org/toc/1932-6203Vascular endothelial growth factor (VEGF) is up-regulated during mesothelial to mesenchymal transition (MMT) and has been associated with peritoneal membrane dysfunction in peritoneal dialysis (PD) patients. It has been shown that normal and malignant mesothelial cells (MCs) express VEGF receptors (VEGFRs) and co-receptors and that VEGF is an autocrine growth factor for mesothelioma. Hence, we evaluated the expression patterns and the functional relevance of the VEGF/VEGFRs/co-receptors axis during the mesenchymal conversion of MCs induced by peritoneal dialysis. Omentum-derived MCs treated with TGF-β1 plus IL-1β (in vitro MMT) and PD effluent-derived MCs with non-epithelioid phenotype (ex vivo MMT) showed down-regulated expression of the two main receptors Flt-1/VEGFR-1 and KDR/VEGFR-2, whereas the co-receptor neuropilin-1 (Nrp-1) was up-regulated. The expression of the Nrp-1 ligand semaphorin-3A (Sema-3A), a functional VEGF competitor, was repressed throughout the MMT process. These expression pattern changes were accompanied by a reduction of the proliferation capacity and by a parallel induction of the invasive capacity of MCs that had undergone an in vitro or ex vivo MMT. Treatment with neutralizing anti-VEGF or anti-Nrp-1 antibodies showed that these molecules played a relevant role in cellular proliferation only in naïve omentum-derived MCs. Conversely, treatment with these blocking antibodies, as well as with recombinant Sema-3A, indicated that the switched VEGF/VEGFRs/co-receptors axis drove the enhanced invasion capacity of MCs undergoing MMT. In conclusion, the expression patterns of VEGFRs and co-receptors change in MCs during MMT, which in turn would determine their behaviour in terms of proliferation and invasion in response to VEGF.María Luisa Pérez-LozanoPilar SandovalAngela Rynne-VidalAbelardo AguileraJosé Antonio Jiménez-HeffernanPatricia Albar-VizcaínoPedro L MajanoJosé Antonio Sánchez-TomeroRafael SelgasManuel López-CabreraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60776 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María Luisa Pérez-Lozano Pilar Sandoval Angela Rynne-Vidal Abelardo Aguilera José Antonio Jiménez-Heffernan Patricia Albar-Vizcaíno Pedro L Majano José Antonio Sánchez-Tomero Rafael Selgas Manuel López-Cabrera Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
description	Vascular endothelial growth factor (VEGF) is up-regulated during mesothelial to mesenchymal transition (MMT) and has been associated with peritoneal membrane dysfunction in peritoneal dialysis (PD) patients. It has been shown that normal and malignant mesothelial cells (MCs) express VEGF receptors (VEGFRs) and co-receptors and that VEGF is an autocrine growth factor for mesothelioma. Hence, we evaluated the expression patterns and the functional relevance of the VEGF/VEGFRs/co-receptors axis during the mesenchymal conversion of MCs induced by peritoneal dialysis. Omentum-derived MCs treated with TGF-β1 plus IL-1β (in vitro MMT) and PD effluent-derived MCs with non-epithelioid phenotype (ex vivo MMT) showed down-regulated expression of the two main receptors Flt-1/VEGFR-1 and KDR/VEGFR-2, whereas the co-receptor neuropilin-1 (Nrp-1) was up-regulated. The expression of the Nrp-1 ligand semaphorin-3A (Sema-3A), a functional VEGF competitor, was repressed throughout the MMT process. These expression pattern changes were accompanied by a reduction of the proliferation capacity and by a parallel induction of the invasive capacity of MCs that had undergone an in vitro or ex vivo MMT. Treatment with neutralizing anti-VEGF or anti-Nrp-1 antibodies showed that these molecules played a relevant role in cellular proliferation only in naïve omentum-derived MCs. Conversely, treatment with these blocking antibodies, as well as with recombinant Sema-3A, indicated that the switched VEGF/VEGFRs/co-receptors axis drove the enhanced invasion capacity of MCs undergoing MMT. In conclusion, the expression patterns of VEGFRs and co-receptors change in MCs during MMT, which in turn would determine their behaviour in terms of proliferation and invasion in response to VEGF.
format	article
author	María Luisa Pérez-Lozano Pilar Sandoval Angela Rynne-Vidal Abelardo Aguilera José Antonio Jiménez-Heffernan Patricia Albar-Vizcaíno Pedro L Majano José Antonio Sánchez-Tomero Rafael Selgas Manuel López-Cabrera
author_facet	María Luisa Pérez-Lozano Pilar Sandoval Angela Rynne-Vidal Abelardo Aguilera José Antonio Jiménez-Heffernan Patricia Albar-Vizcaíno Pedro L Majano José Antonio Sánchez-Tomero Rafael Selgas Manuel López-Cabrera
author_sort	María Luisa Pérez-Lozano
title	Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
title_short	Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
title_full	Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
title_fullStr	Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
title_full_unstemmed	Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
title_sort	functional relevance of the switch of vegf receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a2e5237e824946a891c52bbbd29b9112
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Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition.

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