Non-canonical NFκB activation promotes chemokine expression in podocytes

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dc.contributor.author Valiño-Rivas, Lara
dc.contributor.author Gonzalez-Lafuente, Laura
dc.contributor.author Sanz, Ana Belén
dc.contributor.author Ruiz-Ortega, Marta
dc.contributor.author Ortiz, Alberto
dc.contributor.author Sanchez-Niño, María D.
dc.contributor.other UAM. Departamento de Medicina es_ES
dc.contributor.other Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD) es_ES
dc.date.accessioned 2017-04-06T16:59:26Z
dc.date.available 2017-04-06T16:59:26Z
dc.date.issued 2016-06-29
dc.identifier.citation Scientific Reports 6 (2016): 28857 en_US
dc.identifier.issn 2045-2322 es_ES
dc.identifier.uri http://hdl.handle.net/10486/677928
dc.description.abstract TNF-like weak inducer of apoptosis (TWEAK) receptor Fn14 is expressed by podocytes and Fn14 deficiency protects from experimental proteinuric kidney disease. However, the downstream effectors of TWEAK/Fn14 in podocytes are poorly characterized. We have explored TWEAK activation of non-canonical NFκB signaling in cultured podocytes. In cultured podocytes, TWEAK increased the expression of the chemokines CCL21, CCL19 and RANTES in a time-dependent manner. The inhibitor of canonical NFκB activation parthenolide inhibited the CCL19 and the early RANTES responses, but not the CCL21 or late RANTES responses. In this regard, TWEAK induced non-canonical NFκB activation in podocytes, characterized by NFκB2/p100 processing to NFκB2/p52 and nuclear migration of RelB/p52. Silencing by a specific siRNA of NIK, the upstream kinase of the non-canonical NFκB pathway, prevented CCL21 upregulation but did not modulate CCL19 or RANTES expression in response to TWEAK, thus establishing CCL21 as a non-canonical NFκB target in podocytes. Increased kidney Fn14 and CCL21 expression was also observed in rat proteinuric kidney disease induced by puromycin, and was localized to podocytes. In conclusion, TWEAK activates the non-canonical NFκB pathway in podocytes, leading to upregulation of CCL21 expression. The non-canonical NFκB pathway should be explored as a potential therapeutic target in proteinuric kidney disease. en_US
dc.description.sponsorship Grants support: FEDER funds and FIS ISCIII-RETIC REDinREN RD12/0021, PI15/00298, PI13/00047, CP14/00133, CP12/03262, Spanish Society of Nephrology, FRIAT-IRSIN, Comunidad de Madrid (CIFRA S2010/ BMD-2378), CYTED IBERERC, Programa Intensificación Actividad Investigadora (ISCIII) to AO, Miguel Servet to MDSN and ABS and FIS to LVR and LGL en_US
dc.format.extent 12 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Nature Publishing Group en_US
dc.relation.ispartof Scientific Reports en_US
dc.subject.other Podocytes en_US
dc.subject.other Activation of non-canonical NFκB en_US
dc.subject.other Expression en_US
dc.title Non-canonical NFκB activation promotes chemokine expression in podocytes en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion http://dx.doi.org/10.1038/srep28857 es_ES
dc.identifier.doi 10.1038/srep28857 es_ES
dc.identifier.publicationfirstpage 28857-1 es_ES
dc.identifier.publicationissue 6 es_ES
dc.identifier.publicationlastpage 28857-12 es_ES
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2378/CIFRA es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess en


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