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dc.contributor.authorSanchez-Iranzo, Hector 
dc.contributor.authorGalardi-Castilla, Maria 
dc.contributor.authorSanz-Morejon, Andres 
dc.contributor.authorGonzalez-Rosa, Juan Manuel 
dc.contributor.authorCosta, Ricardo 
dc.contributor.authorErnst, Alexander
dc.contributor.authorSainz de Aja, Julio 
dc.contributor.authorLanga, Xavier
dc.contributor.authorMercader, Nadia 
dc.date.accessioned2018-11-22T08:10:52Z
dc.date.available2018-11-22T08:10:52Z
dc.date.issued2018
dc.identifierISI:000430191900069
dc.identifier.citationProc Natl Acad Sci U S A. 2018; 115(16):4188-93
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6676
dc.description.abstractIn the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b- and collagen 1alpha2 (col1a2)-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells impaired cardiomyocyte proliferation. We conclude that ECMproducing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.
dc.description.sponsorshipWe are grateful to the Animal Facility, Histology, Microscopy, Cellomics, Bioinformatics, and Genomics units of the CNIC, and the Microscopy Imaging Center of the University of Bern. We thank C. Helker for sharing reagents, and O. Kanisicak for discussions. H.S.-I. and N.M. were funded by the Spanish Ministry of Economy and Competitiveness (MINECO) by Grants FPU12/03007 and BFU2014-56970-P, Plan Estatal 2013-2016, Programa Estatal de I+D+i: Proyectos I+D+i 2016, and Fondo Europeo de Desarrollo Regional. N.M. is supported by Swiss National Science Foundation Grant 31003A\_159721 and ERC Starting Grant 337703-Zebra-Heart. A.E. is funded through ANR-SNF Project 320030E-164245 (to N.M.). The CNIC is supported by MINECO and the ProCNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO Award SEV-2015-0505).
dc.language.isoeng
dc.publisherNational Academy of Sciences 
dc.type.hasVersionVoR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHeart regeneration
dc.subjectFibroblast inactivation
dc.subjectZebrafish
dc.subjectFibrosis
dc.subjectCardiomyocyte proliferation
dc.titleTransient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart
dc.typejournal article
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID29610343
dc.format.volume115
dc.format.page4188-4193
dc.identifier.doi10.1073/pnas.1716713115
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderSwiss National Science Foundation 
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderUnión Europea. Comisión Europea 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewed
dc.identifier.journalProceedings of the National Academy of Sciences
dc.repisalud.orgCNICCNIC::Grupos de investigación::Desarrollo del Epicardio y su Papel en la Regeneración
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genómica Funcional
dc.repisalud.institucionCNIC
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU12/03007es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BFU2014-56970-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/337703/EUes_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional