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dc.contributor.author | Iavarone, Francescopaolo | |
dc.contributor.author | Guardiola, Ombretta | |
dc.contributor.author | Scagliola, Alessandra | |
dc.contributor.author | Andolfi, Gennaro | |
dc.contributor.author | Esposito, Federica | |
dc.contributor.author | Serrano, Antonio L | |
dc.contributor.author | Perdiguero, Eusebio | |
dc.contributor.author | Brunelli, Silvia | |
dc.contributor.author | Munoz-Canoves, Pura | |
dc.contributor.author | Minchiotti, Gabriella | |
dc.date.accessioned | 2020-03-25T14:52:28Z | |
dc.date.available | 2020-03-25T14:52:28Z | |
dc.date.issued | 2020-02-27 | |
dc.identifier.citation | EMBO Rep. 2020:e49075 | es_ES |
dc.identifier.issn | 1469-221X | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9332 | |
dc.description.abstract | Macrophages are characterized by a high plasticity in response to changes in tissue microenvironment, which allows them to acquire different phenotypes and to exert essential functions in complex processes, such as tissue regeneration. Here, we report that the membrane protein Cripto plays a key role in shaping macrophage plasticity in skeletal muscle during regeneration and disease. Conditional deletion of Cripto in the myeloid lineage (CriptoMy-LOF ) perturbs MP plasticity in acutely injured muscle and in mouse models of Duchenne muscular dystrophy (mdx). Specifically, CriptoMy-LOF macrophages infiltrate the muscle, but fail to properly expand as anti-inflammatory CD206+ macrophages, which is due, at least in part, to aberrant activation of TGFβ/Smad signaling. This reduction in macrophage plasticity disturbs vascular remodeling by increasing Endothelial-to-Mesenchymal Transition (EndMT), reduces muscle regenerative potential, and leads to an exacerbation of the dystrophic phenotype. Thus, in muscle-infiltrating macrophages, Cripto is required to promote the expansion of the CD206+ anti-inflammatory macrophage type and to restrict the EndMT process, providing a direct functional link between this macrophage population and endothelial cells. | es_ES |
dc.description.sponsorship | We thank the Animal House, Integrated Microscopy, and FACS Facilities of IGB-CNR Naples. We kindly thank Prof. Michael Shen for providing the Cripto flx/flx mice. This work is supported by AFM 21534, SATIN-POR Campania FESR 2014/2020, Italian Ministry of Education-University-Research (CTN01_00177 Cluster ALISEI_IRMI; PRIN 2017XJ38A4) and AIRC (IG20736) to GM; and by the Spanish Ministry of Science and Innovation, Spain [grants SAF2015-67369-R, RTI2018-096068-B-I00 and SAF2015-70270-REDT, a María de Maeztu Unit of Excellence award to UPF (MDM-2014-0370), and a Severo Ochoa Center ofExcellence award to the CNIC (SEV-2015-0505)], the UPF-CNIC collaborationagreement, ERC-2016-AdG-741966, La Caixa-HEALTH (HR17-00040), MDA,UPGRADE-H2020-825825, AFM653, and DPP-E. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | EMBO Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Cripto | es_ES |
dc.subject | Duchenne muscular dystrophy | es_ES |
dc.subject | Endothelial-to-Mesenchymal Transition | es_ES |
dc.subject | Macrophage plasticity | es_ES |
dc.subject | Skeletal muscle regeneration | es_ES |
dc.title | Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 32107853 | es_ES |
dc.format.page | e49075 | es_ES |
dc.identifier.doi | 10.15252/embr.201949075 | es_ES |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Unión Europea. Comisión Europea | |
dc.contributor.funder | Fundación La Caixa | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1469-3178 | es_ES |
dc.relation.publisherversion | https://doi.org/10.15252/embr.201949075 | es_ES |
dc.identifier.journal | EMBO reports | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Laboratorio de Regeneración Tisular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SEV-2015-0505 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/MDM-2014-0370 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-67369-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/RTI2018-096068-B-I00 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2015-70270-REDT | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/825825 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/741966 | es_ES |
dc.rights.accessRights | open access | es_ES |