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dc.contributor.author | Strippoli, Raffaele | |
dc.contributor.author | Loureiro, Jesus | |
dc.contributor.author | Moreno, Vanessa | |
dc.contributor.author | Benedicto, Ignacio | |
dc.contributor.author | Perez Lozano, Maria Luisa | |
dc.contributor.author | Barreiro, Olga | |
dc.contributor.author | Pellinen, Teijo | |
dc.contributor.author | Minguet, Susana | |
dc.contributor.author | Foronda, Miguel | |
dc.contributor.author | Osteso, Maria Teresa | |
dc.contributor.author | Calvo, Enrique | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Lopez Cabrera, Manuel | |
dc.contributor.author | del Pozo, Miguel Angel | |
dc.date.accessioned | 2017-12-01T07:37:27Z | |
dc.date.available | 2017-12-01T07:37:27Z | |
dc.date.issued | 2015 | |
dc.identifier | ISI:000347339600008 | |
dc.identifier.citation | EMBO Mol Med. 2015; 7(1):102-23 | |
dc.identifier.issn | 1757-4676 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/5527 | |
dc.description.abstract | Peritoneal dialysis (PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition (EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1(-/-) mice showed increased EMT, thickness, and fibrosis. Exposure of Cav1(-/-) mice to PD fluids further increased peritoneal membrane thickness, altered permeability, and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma. High-throughput quantitative proteomics revealed increased abundance of collagens, FN, and laminin, as well as proteins related to TGF-beta activity in matrices derived from Cav1(-/-) cells. Lack of Cav1 was associated with hyperactivation of a MEK-ERK1/2-Snail-1 pathway that regulated the Smad2-3/Smad1-5-8 balance. Pharmacological blockade of MEK rescued E-cadherin and ZO-1 inter-cellular junction localization, reduced fibrosis, and restored peritoneal function in Cav1(-/-) mice. Moreover, treatment of human PD-patient-derived MCs with drugs increasing Cav1 levels, as well as ectopic Cav1 expression, induced re-acquisition of epithelial features. This study demonstrates a pivotal role of Cav1 in the balance of epithelial versus mesenchymal state and suggests targets for the prevention of fibrosis during PD. | |
dc.description.sponsorship | We thank Dr. Kurzchalia, Dr. Pol, and Dr. Lisanti for providing us MEFs from WT and Cav1<SUP>-/-</SUP> mice. We thank Dr. Valeria Caiolfa, head of CNIC Microscopy unit, and Elvira Arza and Antonio Manuel Santos Beneit for technical assistance. We thank Cecilia Battistelli and Marta Loureiro Lopez por technical assistance in molecular biology and proteomics, respectively. This work was supported by grants from the MINECO (Spanish Ministry of Economy and Competitivity) to MADP (SAF2008-02100, SAF2011-25047 and CONSOLIDER CSD2009-00016) and to MLC (SAF2010-21249 and SAF2013-47611R), and from Fundacio la Marato TV3 (674/C/2013) to MADP. Raffaele Strippoli was supported by a Rio Hortega Contract (Instituto de Salud Carlos III). Ignacio Benedicto was recipient of a CIBERehd fellowship (Spanish Ministry of Health and Consumer Affairs). Susana Minguet was supported by the Ramon y Cajal program (Spanish Ministry of Science and Innovation). Simon Bartlett (CNIC) provided editorial assistance. The CNIC is supported by MINECO and the Pro-CNIC Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | |
dc.language.iso | eng | |
dc.publisher | Wiley | |
dc.type.hasVersion | VoR | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Caveolin-1 | |
dc.subject | Epithelial-mesenchymal transition | |
dc.subject | Fibrosis | |
dc.subject | MEK-ERK1/2 pathway | |
dc.subject | Peritoneal dialysis | |
dc.subject | ENDOTHELIAL GROWTH-FACTOR | |
dc.subject | E-CADHERIN EXPRESSION | |
dc.subject | MAP KINASE PATHWAY | |
dc.subject | NF-KAPPA-B | |
dc.subject | MESOTHELIAL CELLS | |
dc.subject | TGF-BETA | |
dc.subject | TRANSCRIPTIONAL ACTIVITY | |
dc.subject | QUANTITATIVE PROTEOMICS | |
dc.subject | SCAFFOLDING DOMAIN | |
dc.subject | PULMONARY DEFECTS | |
dc.title | Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis | |
dc.type | journal article | |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 25550395 | |
dc.format.volume | 7 | |
dc.format.page | 102-123 | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Centro de Investigación Biomédica en Red - CIBEREHD (Enfermedades Hepáticas y Digestivas) | |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | |
dc.contributor.funder | Fundación ProCNIC | |
dc.description.peerreviewed | Sí | |
dc.identifier.e-issn | 1757-4684 | |
dc.relation.publisherversion | https://doi.org/10.15252/emmm.201404127 | |
dc.identifier.journal | EMBO Molecular Medicine | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Señalización por Integrinas | |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Proteómica / Metabolómica | |
dc.repisalud.institucion | CNIC | |
dc.relation.projectID | MINECO/ICTI2013-2016/SAF2013-47611R | es_ES |
dc.rights.accessRights | open access | es_ES |