Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/24352
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dc.contributor.authorOrtiz, Albertoen_UK
dc.contributor.authorHusi, Holgeren_UK
dc.contributor.authorGonzalez-Lafuente, Lauraen_UK
dc.contributor.authorValino-Rivas, Laraen_UK
dc.contributor.authorFresno, Manuelen_UK
dc.contributor.authorSanz, Ana Belenen_UK
dc.contributor.authorMullen, Williamen_UK
dc.contributor.authorAlbalat, Amayaen_UK
dc.contributor.authorMezzano, Sergioen_UK
dc.contributor.authorVlahou, Antoniaen_UK
dc.contributor.authorMischak, Haralden_UK
dc.contributor.authorSanchez-Nino, Maria Doloresen_UK
dc.date.accessioned2017-04-21T01:57:04Z-
dc.date.available2017-04-21T01:57:04Z-
dc.date.issued2017-03en_UK
dc.identifier.urihttp://hdl.handle.net/1893/24352-
dc.description.abstractAn improved understanding of pathogenic pathways may identify novel acute kidney injury (AKI) therapeutic approaches. Unbiased LC-MS/MS protein expression profiling combined with focused data mining identified MAP3K14 and non-canonical NFκB activation at the crossroads of the enriched pathways MAPK, ubiquitin-mediated proteolysis, chemokines, NFκB and apoptosis in the kidney cortex of experimental toxic AKI. In AKI the upstream kinase MAP3K14, the NFκB DNA binding heterodimer RelB/NFκB2, and proteins involved in NFκB2 p100 ubiquitination and proteasomal processing to p52, such as Ube2m and cullin1 were up-regulated. Immunohistochemistry localized MAP3K14 expression to tubular cells in experimental and human AKI. In vivo evidence of MAP3K14 activation in experimental folic acid-induced AKI consisted of NFκB2 p100 processing to p52, nuclear location and DNA binding of RelB and NFκB2. MAP3K14 activity-deficient aly/aly mice were protected from kidney dysfunction, inflammation and apoptosis in AKI induced by folic acid and from lethality in cisplatin-induced AKI. MAP3K14 siRNA targeting in cultured tubular cells decreased inflammation and cell death. Bone marrow transplantation experiments where consistent with a protective effect of renal cell MAP3K14 targeting. Cell culture and in vivo studies identified chemokines MCP-1, RANTES and CXCL10 as MAP3K14 targets in tubular cells, thus identifying potential mediators of the deleterious effect of MAP3K14 in kidney injury. In conclusion, MAP3K14 promotes kidney injury through promotion of inflammation and cell death and is a promising novel therapeutic target.en_UK
dc.language.isoenen_UK
dc.publisherAmerican Society of Nephrologyen_UK
dc.relationOrtiz A, Husi H, Gonzalez-Lafuente L, Valino-Rivas L, Fresno M, Sanz AB, Mullen W, Albalat A, Mezzano S, Vlahou A, Mischak H & Sanchez-Nino MD (2017) Mitogen-Activated Protein Kinase 14 Promotes AKI. Journal of the American Society of Nephrology, 28 (3), pp. 823-836. https://doi.org/10.1681/ASN.2015080898en_UK
dc.rightsPublisher policy allows this work to be made available in this repository. Published in Journal of the American Society of Nephrology by American Society of Nephrology. The original publication is available at: http://dx.doi.org/10.1681/ASN.2015080898en_UK
dc.subjectacute kidney injuryen_UK
dc.subjectapoptosisen_UK
dc.subjectinflammationen_UK
dc.subjectMAP3K14en_UK
dc.subjectNIKen_UK
dc.subjectnon-canonical NFκBen_UK
dc.subjecttissue proteomicsen_UK
dc.titleMitogen-Activated Protein Kinase 14 Promotes AKIen_UK
dc.typeJournal Articleen_UK
dc.identifier.doi10.1681/ASN.2015080898en_UK
dc.identifier.pmid27620989en_UK
dc.citation.jtitleJournal of the American Society of Nephrologyen_UK
dc.citation.issn1533-3450en_UK
dc.citation.issn1046-6673en_UK
dc.citation.volume28en_UK
dc.citation.issue3en_UK
dc.citation.spage823en_UK
dc.citation.epage836en_UK
dc.citation.publicationstatusPublisheden_UK
dc.citation.peerreviewedRefereeden_UK
dc.type.statusAM - Accepted Manuscripten_UK
dc.type.statusAM - Accepted Manuscripten_UK
dc.type.statusAM - Accepted Manuscripten_UK
dc.author.emailamaya.albalat@stir.ac.uken_UK
dc.citation.date12/09/2016en_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationComplex Systems - LEGACYen_UK
dc.contributor.affiliationUniversidad Austral de Chileen_UK
dc.contributor.affiliationBiomedical Research Foundation Academy of Athens (BRFAA)en_UK
dc.contributor.affiliationUniversity of Glasgowen_UK
dc.contributor.affiliationUniversidad Autonoma de Madriden_UK
dc.identifier.isiWOS:000395049000014en_UK
dc.identifier.wtid551615en_UK
dc.contributor.orcid0000-0002-8606-2995en_UK
dc.date.accepted2016-07-28en_UK
dc.date.filedepositdate2016-08-26en_UK
Appears in Collections:Aquaculture Journal Articles

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