Functional relevance of the switch of VEGF receptors/co-receptors during peritoneal dialysis-induced mesothelial to mesenchymal transition
EntityUAM. Departamento de Medicina
PublisherPublic Library of Science
10.1371/journal.pone.0060776Plos One 8.4 (2013): e60776
Funded byThis work was supported by grant SAF2010-21249 from the ‘‘Ministerio de Economía y Competitividad’’ to M.L.C. and by grant S2010/BMD-2321 from ‘‘Comunidad Autónoma de Madrid’’ to M.L.C. and R.S. This work was also partially supported by grants PI 09/0776 from ‘‘Fondo de Investigaciones Sanitarias’’ to A.A., and RETICS 06/0016 (REDinREN, Fondos FEDER, EU) to R.S.
ProjectComunidad de Madrid. S2010/BMD-2321/FIBROTEAM
SubjectsAntibodies; Epithelial Cells; Interleukin-1beta; Peritoneal Dialysis; Semaphorin-3A; Gene Expression Regulation; Medicina
Rights© 2013 Pérez-Lozano et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Pérez-Lozano, María Luisa - Sandoval, Pilar - Rynne-Vidal, Ángela - Aguilera, Abelardo I. - Jiménez-Heffernan, José Antonio - Albar-Vizcaíno, Patricia - Majano, Pedro Lorenzo - Sánchez-Tomero, José Antonio - Selgas Gutiérrez, Rafael - López-Cabrera, Manuel
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