TWEAK increases CD74 expression and sensitizes to DDT proinflammatory actions in tubular cells

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dc.contributor.author Valiño-Rivas, Lara
dc.contributor.author Cuarental, Leticia
dc.contributor.author Grana, Osvaldo
dc.contributor.author Bucala, Richard
dc.contributor.author Leng, Lin
dc.contributor.author Sanz, Ana
dc.contributor.author Gómez, Gonzalo
dc.contributor.author Ortiz, Alberto
dc.contributor.author Sánchez-Niño, María Dolores
dc.contributor.other UAM. Departamento de Bioquímica es_ES
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 2018-12-19T16:56:01Z
dc.date.available 2018-12-19T16:56:01Z
dc.date.issued 2018-06-20
dc.identifier.citation PLoS ONE 13.6 (2018): e0199391 es_ES
dc.identifier.issn 1932-6203 es_ES
dc.identifier.uri http://hdl.handle.net/10486/686104
dc.description.abstract CD74 is a multifunctional protein and a receptor for Macrophage Migration Inhibitory Factor (MIF) and MIF-2 / D-dopachrome tautomerase (DDT) cytokines, upregulated in diabetic kidney disease. However, the drivers of CD74 expression and DDT function in kidney cells are poorly characterized. TWEAK is a proinflammatory cytokine that promotes kidney injury. We have now identified CD74 gene expression as upregulated in the kidneys in response to systemic TWEAK administration in mice, and have characterized the in vivo CD74 expression and the functional consequences in cultured cells. TWEAK administration to mice resulted in a progressive time-dependent (up to 24h) upregulation of kidney CD74 mRNA (RT-PCR) and protein (Western blot). Furthermore, the CD74 ligands MIF and DDT were also upregulated at the protein level 24h after TWEAK administration. Immunohistochemistry localized the increased CD74, MIF and DDT expression to tubular cells. In cultured tubular cells, TWEAK increased CD74 mRNA and protein expression dose-dependently, with a temporal pattern similar to in vivo. TWEAK-induced CD74 localized to the cell membrane, where it can function as a cytokine receptor. For the first time, we explored the actions of DDT in tubular cells and found that DDT amplified the increase in MCP-1 and RANTES expression in response to TWEAK. By contrast, DDT did not significantly modify TWEAKinduced Klotho downregulation. In conclusion, TWEAK upregulates CD74 and its ligands MIF and DDT in renal tubular cells. This may have functional consequences for kidney injury since DDT amplified the inflammatory response to TWEAK es_ES
dc.description.sponsorship This work was supported by FIS PI15/ 00298, CP14/00133, PI16/02057, PI16/01900, ISCIII-RETIC REDinREN RD016/0009 Fondos FEDER, Sociedad Española de Nefrologia and Programas de actividades de I + D entre grupos de investigación de la Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM. Salary support: FIS Miguel Servet MS14/00133 to MDSN and to ABS, and FIS FI14/00398 to LVR. RB and LL are supported by the US NIH es_ES
dc.format.extent 15 pag. es_ES
dc.format.mimetype application/pdf es_ES
dc.language.iso eng es_ES
dc.publisher Public Library of Science es_ES
dc.relation.ispartof PLos ONE es_ES
dc.rights © 2018 Valiño-Rivas et al. es_ES
dc.subject.other CD74 es_ES
dc.subject.other Protein es_ES
dc.subject.other Macrophage Migration Inhibitory Factor (MIF) es_ES
dc.subject.other Diabetic kidney disease es_ES
dc.subject.other TWEAK es_ES
dc.subject.other DDT es_ES
dc.title TWEAK increases CD74 expression and sensitizes to DDT proinflammatory actions in tubular cells es_ES
dc.type article es_ES
dc.subject.eciencia Medicina es_ES
dc.relation.publisherversion https://doi.org/10.1371/journal. pone.0199391 es_ES
dc.identifier.doi 10.1371/journal. pone.0199391 es_ES
dc.identifier.publicationfirstpage e0199391-1 es_ES
dc.identifier.publicationissue 6 es_ES
dc.identifier.publicationlastpage e0199391-15 es_ES
dc.identifier.publicationvolume 13 es_ES
dc.relation.projectID Gobierno de España. FIS PI15/ 00298 es_ES
dc.relation.projectID Gobierno de España. CP14/00133 es_ES
dc.relation.projectID Gobierno de España. PI16/02057 es_ES
dc.relation.projectID Gobierno de España. PI16/01900 es_ES
dc.relation.projectID Gobierno de España. RD016/0009 es_ES
dc.relation.projectID Comunidad de Madrid. B2017/BMD-3686/CIFRA es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.rights.cc Reconocimiento es_ES
dc.rights.accessRights openAccess es_ES


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