Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle

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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 Sánchez, Antonio L.
• dc.contributor.author Perdiguero, Eusebio, 1968-
• dc.contributor.author Brunelli, Silvia
• dc.contributor.author Muñoz Cánoves, Pura, 1962-
• dc.contributor.author Minchiotti, Gabriella
• dc.date.accessioned 2020-04-16T07:19:39Z
• dc.date.available 2020-04-16T07:19:39Z
• dc.date.issued 2020
• 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.
• dc.description.sponsorship 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 of Excellence award to the CNIC (SEV‐2015‐0505)], the UPF‐CNIC collaboration agreement, ERC‐2016‐AdG‐741966, La Caixa‐HEALTH (HR17‐00040), MDA, UPGRADE‐H2020‐825825, AFM 653, and DPP‐E.
• dc.format.mimetype application/pdf
• dc.identifier.citation Iavarone F, Guardiola O, Scagliola A, Andolfi G, Esposito F, Serrano A, Perdiguero E, Brunelli S, Muñoz-Cánoves P, Minchiotti G. Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle. EMBO Rep. 2020; 21(4):e49075. DOI: 10.15252/embr.201949075
• dc.identifier.doi http://dx.doi.org/10.15252/embr.201949075
• dc.identifier.issn 1469-221X
• dc.identifier.uri http://hdl.handle.net/10230/44231
• dc.language.iso eng
• dc.publisher EMBO Press
• dc.relation.ispartof EMBO Rep. 2020; 21(4):e49075
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015‐67369‐R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018‐096068‐B‐I00
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015‐70270‐REDT
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/741966
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/825825
• dc.rights © 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Cripto
• dc.subject.keyword Duchenne muscular dystrophy
• dc.subject.keyword Endothelial-to-Mesenchymal Transition
• dc.subject.keyword Macrophage plasticity
• dc.subject.keyword Skeletal muscle regeneration
• dc.title Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion