miR-127 Protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3B as miR-127 target

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dc.contributor.author Aguado-Fraile, Elia
dc.contributor.author Ramos, Edurne
dc.contributor.author Sáenz-Morales, David
dc.contributor.author Conde, Elisa
dc.contributor.author Blanco-Sánchez, Ignacio
dc.contributor.author Stamatakis, Konstantinos
dc.contributor.author del Peso, Luis
dc.contributor.author Cuppen, Edwin
dc.contributor.author Brüne, Bernhard
dc.contributor.author García Bermejo, María Laura
dc.contributor.other UAM. Departamento de Bioquímica es_ES
dc.date.accessioned 2015-05-12T08:21:55Z
dc.date.available 2015-05-12T08:21:55Z
dc.date.issued 2012-09-04
dc.identifier.citation Plos One 7.9 (2012): e44305 en_US
dc.identifier.issn 1932-6203 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/666124
dc.description.abstract Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia. Here, we have identified several miRNAs involved in the response of the proximal tubule cell to I/R. Microarrays and RT-PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in vitro demonstrated that miR-127 is induced during ischemia and also during reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia Inducible Factor-1alpha (HIF-1α) stabilization. Moreover, miR-127 is involved in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR-127 maintains focal adhesion complex assembly and the integrity of tight junctions. miR-127 also regulates intracellular trafficking since miR-127 interference promotes dextran-FITC uptake. In fact, we have identified the Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of miR-127 in rat proximal tubule cells. In summary, we have described a novel role of miR-127 in cell adhesion and its regulation by HIF-1α. We also identified for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as key mediators of proximal epithelial tubule cell response to I/R with potential al application in renal ischemic damage management en_US
dc.description.sponsorship This work was supported by grant FIS PS09/02183 funding by Instituto de Salud Carlos III and Ayuda Intramural Fundación para la Investigación en Biomedicina del Hospital Universitario Ramón y Cajal 122/2009 en_US
dc.format.extent 14 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Public Library of Science en_US
dc.relation.ispartof Plos One en_US
dc.rights © 2012 Aguado-Fraile et al. es_ES
dc.subject.other Biological Transpor en_US
dc.subject.other Sprague-Dawley en_US
dc.subject.other MicroRNAs en_US
dc.subject.other Kinesin en_US
dc.subject.other Reperfusion Injury en_US
dc.title miR-127 Protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3B as miR-127 target en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.identifier.doi 10.1371/journal.pone.0044305 es_ES
dc.identifier.publicationfirstpage e44305 es_ES
dc.identifier.publicationissue 9 es_ES
dc.identifier.publicationlastpage e44305 es_ES
dc.identifier.publicationvolume 7 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en
dc.authorUAM Peso Ovalle, Luis (260044)
dc.authorUAM Stamatakis Andriani, Konstantinos (264078)

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