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dc.contributor.authorAlonso-Herranz, Laura 
dc.contributor.authorSahun-Español, Alvaro
dc.contributor.authorParedes, Ana
dc.contributor.authorGonzalo, Pilar 
dc.contributor.authorGkontra, Polyxeni 
dc.contributor.authorNunez, Vanessa 
dc.contributor.authorClemente, Cristina 
dc.contributor.authorCedenilla, Marta 
dc.contributor.authorVillalba-Orero, Maria 
dc.contributor.authorInserte, Javier
dc.contributor.authorGarcia-Dorado, David
dc.contributor.authorArroyo, Alicia G 
dc.contributor.authorRicote, Mercedes 
dc.date.accessioned2021-06-23T08:30:25Z
dc.date.available2021-06-23T08:30:25Z
dc.date.issued2020-10
dc.identifier.citationElife. 2020; 9:e57920es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13182
dc.description.abstractMacrophages (Mφs) produce factors that participate in cardiac repair and remodeling after myocardial infarction (MI); however, how these factors crosstalk with other cell types mediating repair is not fully understood. Here we demonstrated that cardiac Mφs increased the expression of Mmp14 (MT1-MMP) 7 days post-MI. We selectively inactivated the Mmp14 gene in Mφs using a genetic strategy (Mmp14f/f:Lyz2-Cre). This conditional KO (MAC-Mmp14 KO) resulted in attenuated post-MI cardiac dysfunction, reduced fibrosis, and preserved cardiac capillary network. Mechanistically, we showed that MT1-MMP activates latent TGFβ1 in Mφs, leading to paracrine SMAD2-mediated signaling in endothelial cells (ECs) and endothelial-to-mesenchymal transition (EndMT). Post-MI MAC-Mmp14 KO hearts contained fewer cells undergoing EndMT than their wild-type counterparts, and Mmp14-deficient Mφs showed a reduced ability to induce EndMT in co-cultures with ECs. Our results indicate the contribution of EndMT to cardiac fibrosis and adverse remodeling post-MI and identify Mφ MT1-MMP as a key regulator of this process.es_ES
dc.description.sponsorshipThis study was supported by grants from the Spanish Ministry of Science, Innovation and Universities (SAF2017-90604-REDT-NurCaMein, RTI2018-095928-BI00 to M.R.; SAF2017-83229-R to A.G.A.), Comunidad de Madrid (MOIR-B2017/BMD-3684) to M.R, and La Marató de TV3 Foundation to D.G.D, A.G.A., and M.R.. L.A.H. is funded by a fellowship from La Caixa-CNIC. A.S.E. is supported by La Residencia de Estudiantes and funded by a fellowship from La Caixa and from a partnership between FORD-España and Apadrina La Ciencia. The CNIC is supported by the MCNU and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publishereLife Sciences Publicationses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshEpithelial-Mesenchymal Transition es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCollagen es_ES
dc.subject.meshDisease Models, Animales_ES
dc.subject.meshEndothelium, Vascular es_ES
dc.subject.meshFemale es_ES
dc.subject.meshFibrosis es_ES
dc.subject.meshFlow Cytometry es_ES
dc.subject.meshGene Expression Regulation es_ES
dc.subject.meshHEK293 Cells es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMacrophages es_ES
dc.subject.meshMale es_ES
dc.subject.meshMatrix Metalloproteinase 14 es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshMice, Knockout es_ES
dc.subject.meshMicrocirculation es_ES
dc.subject.meshMyocardial Infarction es_ES
dc.subject.meshPhenotype es_ES
dc.subject.meshReperfusion Injury es_ES
dc.subject.meshTransforming Growth Factor beta1 es_ES
dc.subject.meshVentricular Dysfunction, Left es_ES
dc.titleMacrophages promote endothelial-to-mesenchymal transition via MT1-MMP/TGFβ1 after myocardial infarction.es_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID33063665es_ES
dc.format.volume9es_ES
dc.format.pagee57920es_ES
dc.identifier.doi10.7554/eLife.57920es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderComunidad de Madrides_ES
dc.contributor.funderFundación La Mataró TV3es_ES
dc.contributor.funderFundación La Caixaes_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2050-084Xes_ES
dc.relation.publisherversionhttps://doi.org/10.7554/eLife.57920es_ES
dc.identifier.journaleLifees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización de los Receptores Nucleareses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamaciónes_ES
dc.repisalud.institucionCNICes_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2017-90604-REDT-NurCaMeines_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RTI2018-095928-BI00es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2017-83229-Res_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/MOIR-B2017/BMD-3684es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES


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Atribución 4.0 Internacional
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