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Midkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration.

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dc.contributor.authorGrivas, Dimitrios
dc.contributor.authorGonzález-Rajal, Álvaro
dc.contributor.authorde la Pompa, José Luis
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderFundación BBVAes_ES
dc.contributor.funderFundación La Marató TV3es_ES
dc.contributor.funderCardioNeTes_ES
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)es_ES
dc.contributor.funderInstituto de Salud Carlos IIIes_ES
dc.contributor.funderFundación ProCNICes_ES
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)es_ES
dc.date.accessioned2022-12-22T12:01:18Z
dc.date.available2022-12-22T12:01:18Z
dc.date.issued2021
dc.description.abstractUnlike the hearts of mammals, the adult zebrafish heart regenerates after injury. Heart cryoinjury in zebrafish triggers the formation of a fibrotic scar that gradually degrades, leading to regeneration. Midkine-a (Mdka) is a multifunctional cytokine that is activated after cardiac injury. Here, we investigated the role of mdka in zebrafish heart regeneration. We show that mdka expression was induced at 1-day post-cryoinjury (dpci) throughout the epicardial layer, whereas by 7 dpci expression had become restricted to the epicardial cells covering the injured area. To study the role of mdka in heart regeneration, we generated mdka-knock out (KO) zebrafish strains. Analysis of injured hearts showed that loss of mdka decreased endothelial cell proliferation and resulted in an arrest in heart regeneration characterized by retention of a collagenous scar. Transcriptional analysis revealed increases in collagen transcription and intense TGFβ signaling activity. These results reveal a critical role for mdka in fibrosis regulation during heart regeneration.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThis study was supported by Grants PID2019-104776RB-I00, CB16/11/00399 (CIBER CV) and RD16/0011/0021 (TERCEL) from the Spanish Ministry of Science, Innovation and Universities (MCIU) and Grants from the Fundación BBVA (Ref.: BIO14_298), Fundación La Marató (Ref.: 20153431) and the European Commission through CardioNeT (Ref.: 28600) from the European Commission to JLP. DG held a Ph.D. fellowship linked to the Grant CardioNeT grant. The cost of this publication was supported in part with funds from the European Regional Development Fund. The CNIC was supported by the Instituto de Salud Carlos III (ISCIII), the MCIU and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505).es_ES
dc.format.page669439es_ES
dc.format.volume9es_ES
dc.identifier.citationCell Dev Biol. 2021 May 7;9:669439es_ES
dc.identifier.doi10.3389/fcell.2021.669439es_ES
dc.identifier.issn2296-634Xes_ES
dc.identifier.journalFrontiers in cell and developmental biologyes_ES
dc.identifier.pubmedID34026760es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/15380
dc.language.isoenges_ES
dc.publisherFrontiers Mediaes_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PID2019-104776RB-I00es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RD16/0011/0021es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/BIO14_298es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/FundaciónLaMarato/20153431es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.publisherversiondoi: 10.3389/fcell.2021.669439es_ES
dc.repisalud.institucionCNICes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización Intercelular durante el Desarrollo y la Enfermedad Cardiovasculares_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleMidkine-a Regulates the Formation of a Fibrotic Scar During Zebrafish Heart Regeneration.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublication2d4870f0-8161-4c0b-99ba-0216ec1fd963
relation.isAuthorOfPublication.latestForDiscovery2d4870f0-8161-4c0b-99ba-0216ec1fd963

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