Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis

Mesothelial-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...

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Autores: Loureiro, Jesús, Sandoval, Pilar, Del Peso Gilsanz, María Gloria, González-Mateo, Guadalupe Tirma, Fernández-Millara, Vanessa, Santamaría, Beatríz, Bajo Rubio, María Auxiliadora, Sánchez-Tomero, José Antonio, Guerra-Azcona, Gonzalo, Selgas Gutiérrez, Rafael, López-Cabrera, Manuel, Aguilera, Abelardo I.
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/666876
Acceso en línea:http://hdl.handle.net/10486/666876
https://dx.doi.org/10.1371/journal.pone.0061165
Access Level:acceso abierto
Palabra clave:Epithelial-Mesenchymal Transition
Fibrinolysis
Inbred C57BL
Peritoneal Dialysis
Tamoxifen
Medicina
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spelling Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysisLoureiro, JesúsSandoval, PilarDel Peso Gilsanz, María GloriaGonzález-Mateo, Guadalupe TirmaFernández-Millara, VanessaSantamaría, BeatrízBajo Rubio, María AuxiliadoraSánchez-Tomero, José AntonioGuerra-Azcona, GonzaloSelgas Gutiérrez, RafaelLópez-Cabrera, ManuelAguilera, Abelardo I.Epithelial-Mesenchymal TransitionFibrinolysisInbred C57BLPeritoneal DialysisTamoxifenMedicinaMesothelial-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 processThis 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 RSPublic Library of ScienceDepartamento de MedicinaFacultad de Medicina20132013-04-23research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/666876https://dx.doi.org/10.1371/journal.pone.0061165reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6668762026-06-23T12:46:27Z
dc.title.none.fl_str_mv Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
title Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
spellingShingle Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
Loureiro, Jesús
Epithelial-Mesenchymal Transition
Fibrinolysis
Inbred C57BL
Peritoneal Dialysis
Tamoxifen
Medicina
title_short Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
title_full Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
title_fullStr Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
title_full_unstemmed Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
title_sort Tamoxifen ameliorates peritoneal membrane damage by blocking mesothelial to mesenchymal transition in peritoneal dialysis
dc.creator.none.fl_str_mv Loureiro, Jesús
Sandoval, Pilar
Del Peso Gilsanz, María Gloria
González-Mateo, Guadalupe Tirma
Fernández-Millara, Vanessa
Santamaría, Beatríz
Bajo Rubio, María Auxiliadora
Sánchez-Tomero, José Antonio
Guerra-Azcona, Gonzalo
Selgas Gutiérrez, Rafael
López-Cabrera, Manuel
Aguilera, Abelardo I.
author Loureiro, Jesús
author_facet Loureiro, Jesús
Sandoval, Pilar
Del Peso Gilsanz, María Gloria
González-Mateo, Guadalupe Tirma
Fernández-Millara, Vanessa
Santamaría, Beatríz
Bajo Rubio, María Auxiliadora
Sánchez-Tomero, José Antonio
Guerra-Azcona, Gonzalo
Selgas Gutiérrez, Rafael
López-Cabrera, Manuel
Aguilera, Abelardo I.
author_role author
author2 Sandoval, Pilar
Del Peso Gilsanz, María Gloria
González-Mateo, Guadalupe Tirma
Fernández-Millara, Vanessa
Santamaría, Beatríz
Bajo Rubio, María Auxiliadora
Sánchez-Tomero, José Antonio
Guerra-Azcona, Gonzalo
Selgas Gutiérrez, Rafael
López-Cabrera, Manuel
Aguilera, Abelardo I.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Medicina
Facultad de Medicina
dc.subject.none.fl_str_mv Epithelial-Mesenchymal Transition
Fibrinolysis
Inbred C57BL
Peritoneal Dialysis
Tamoxifen
Medicina
topic Epithelial-Mesenchymal Transition
Fibrinolysis
Inbred C57BL
Peritoneal Dialysis
Tamoxifen
Medicina
description Mesothelial-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 process
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-04-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/666876
https://dx.doi.org/10.1371/journal.pone.0061165
url http://hdl.handle.net/10486/666876
https://dx.doi.org/10.1371/journal.pone.0061165
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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