Show simple item record

dc.contributor.authorEsteban, Sergio 
dc.contributor.authorClemente, Cristina 
dc.contributor.authorKoziol, Agnieszka 
dc.contributor.authorGonzalo, Pilar 
dc.contributor.authorRius, Cristina 
dc.contributor.authorMartinez, Fernando 
dc.contributor.authorLinares, Pablo M
dc.contributor.authorChaparro, María
dc.contributor.authorUrzainqui, Ana
dc.contributor.authorAndres, Vicente 
dc.contributor.authorSeiki, Motoharu
dc.contributor.authorGisbert, Javier P
dc.contributor.authorArroyo, Alicia G 
dc.date.accessioned2020-04-20T13:21:54Z
dc.date.available2020-04-20T13:21:54Z
dc.date.issued2020-02
dc.identifier.citationEMBO Mol Med. 2020; 12(2):e10862es_ES
dc.identifier.issn1757-4676es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9631
dc.description.abstractPathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a poorly characterized mechanism involving increased blood flow and splitting of pre-existing capillaries. In this report, mice lacking the protease MT1-MMP in endothelial cells (MT1iΔEC ) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS-induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1-MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C-terminal fragment of MT1-MMP substrate thrombospondin-1 (TSP1) to CD47/αvβ3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti-MT1-MMP inhibitory antibody or a nonamer peptide spanning the αvβ3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1-MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.es_ES
dc.description.sponsorshipThis study was supported by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (SAF2014-52050-R and SAF2017-83229-R to A.G.A). S.E. was recipient of a FPISevero Ochoa fellowship. The CNIC is supported by the Instituto de Salud Carlos III, the Spanish Ministry of Ciencia, Innovación y Universidades, and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherEMBOes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectMT1-MMPes_ES
dc.subjectTSP1es_ES
dc.subjectinflammatory bowel diseasees_ES
dc.subjectintussusceptive angiogenesises_ES
dc.subjectnitric oxidees_ES
dc.titleEndothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axises_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID31793743es_ES
dc.format.volume12es_ES
dc.format.number2es_ES
dc.format.pagee10862es_ES
dc.identifier.doi10.15252/emmm.201910862es_ES
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderFundación ProCNICes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1757-4684es_ES
dc.relation.publisherversionhttps://doi.org/10.15252/emmm.201910862es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Metaloproteinasas de Matriz en Angiogénesis e Inflamaciónes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Fisiopatología Cardiovascular Molecular y Genéticaes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Bioinformáticaes_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-52050-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2017-83229-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Acceso Abierto
Thumbnail

This item appears in the following Collection(s)

Show simple item record

Atribución 4.0 Internacional
This item is licensed under a: Atribución 4.0 Internacional