Show simple item record

dc.contributor.authorLoureiro, Jesús
dc.contributor.authorSandoval, Pilar
dc.contributor.authorDel Peso, Gloria D.
dc.contributor.authorGonzález-Mateo, Guadalupe Tirma
dc.contributor.authorFernández-Millara, Vanessa
dc.contributor.authorSantamaría, Beatríz
dc.contributor.authorBajo Rubio, María Auxiliadora 
dc.contributor.authorSánchez-Tomero, José Antonio
dc.contributor.authorGuerra-Azcona, Gonzalo
dc.contributor.authorSelgas Gutiérrez, Rafael
dc.contributor.authorLópez-Cabrera, Manuel
dc.contributor.authorAguilera, Abelardo I.
dc.contributor.otherUAM. Departamento de Medicinaes_ES
dc.date.accessioned2015-06-17T13:00:50Z
dc.date.available2015-06-17T13:00:50Z
dc.date.issued2013-04-23
dc.identifier.citationPlos One 8.4 (2013): e61165en_US
dc.identifier.issn1932-6203 (online)es_ES
dc.identifier.urihttp://hdl.handle.net/10486/666876
dc.description.abstractMesothelial-to-mesenchymal transition (MMT) is an auto-regulated physiological process of tissue repair that in uncontrolled conditions such as peritoneal dialysis (PD) can lead to peritoneal fibrosis. The maximum expression of peritoneal fibrosis induced by PD fluids and other peritoneal processes is the encapsulating peritoneal sclerosis (EPS) for which no specific treatment exists. Tamoxifen, a synthetic estrogen, has successfully been used to treat retroperitoneal fibrosis and EPS associated with PD. Hence, we used in vitro and animal model approaches to evaluate the efficacy of Tamoxifen to inhibit the MMT as a trigger of peritoneal fibrosis. In vitro studies were carried out using omentum-derived mesothelial cells (MCs) and effluent-derived MCs. Tamoxifen blocked the MMT induced by transforming growth factor (TGF)-β1, as it preserved the expression of E-cadherin and reduced the expression of mesenchymal-associated molecules such as snail, fibronectin, collagen-I, α-smooth muscle actin, and matrix metalloproteinse-2. Tamoxifen-treatment preserved the fibrinolytic capacity of MCs treated with TGF-β1 and decreased their migration capacity. Tamoxifen did not reverse the MMT of non-epitheliod MCs from effluents, but it reduced the expression of some mesenchymal molecules. In mice PD model, we demonstrated that MMT progressed in parallel with peritoneal membrane thickness. In addition, we observed that Tamoxifen significantly reduced peritoneal thickness, angiogenesis, invasion of the compact zone by mesenchymal MCs and improved peritoneal function. Tamoxifen also reduced the effluent levels of vascular endothelial growth factor and leptin. These results demonstrate that Tamoxifen is a therapeutic option to treat peritoneal fibrosis, and that its protective effect is mediated via modulation of the MMT processen_US
dc.description.sponsorshipThis work was supported by grant SAF2010-21249 from the ‘‘Ministerio de Economia y Competitividad’’ to MLC and by grant S2010/BMD-2321 from ‘‘Comunidad Autónoma de Madrid’’ to MLC and RS. This work was also partially supported by grants PI 09/0776 from ‘‘Fondo de Investigaciones Sanitarias’’ to AA, and RETICS 06/0016 (REDinREN, Fondos FEDER, EU) to RSen_US
dc.format.extent15 pag.es_ES
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherPublic Library of Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.rights© 2013 Loureiro et al.es_ES
dc.subject.otherEpithelial-Mesenchymal Transitionen_US
dc.subject.otherFibrinolysisen_US
dc.subject.otherInbred C57BLen_US
dc.subject.otherPeritoneal Dialysisen_US
dc.subject.otherTamoxifenen_US
dc.titleTamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysisen_US
dc.typearticleen
dc.subject.ecienciaMedicinaes_ES
dc.identifier.doi10.1371/journal.pone.0061165es_ES
dc.identifier.publicationfirstpagee61165es_ES
dc.identifier.publicationissue4es_ES
dc.identifier.publicationlastpagee61165es_ES
dc.identifier.publicationvolume8es_ES
dc.relation.projectIDComunidad de Madrid. S2010/BMD-2321/FIBROTEAMes_ES
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.rights.ccReconocimientoes_ES
dc.rights.accessRightsopenAccessen
dc.authorUAMBajo Rubio, María Auxiliadora (261173)
dc.authorUAMSelgas Gutiérrez, Rafael (260574)
dc.facultadUAMFacultad de Medicina
dc.institutoUAMCentro de Biología Molecular Severo Ochoa (CBMSO)
dc.institutoUAMInstituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ)
dc.institutoUAMInstituto de Investigación Sanitaria Hospital Universitario de La Princesa (IIS-Princesa)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record