Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
Non-canonical NFκB activation promotes chemokine expression in podocytes
Entidad
UAM. Departamento de Medicina; Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD)Editor
Nature Publishing GroupFecha de edición
2016-06-29Cita
10.1038/srep28857
Scientific Reports 6 (2016): 28857
ISSN
2045-2322DOI
10.1038/srep28857Financiado por
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 LGLProyecto
Comunidad de Madrid. S2010/BMD-2378/CIFRAVersión del editor
http://dx.doi.org/10.1038/srep28857Materias
Podocytes; Activation of non-canonical NFκB; Expression; MedicinaResumen
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.
Lista de ficheros
Google Scholar:Valiño-Rivas, Lara
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Gonzalez-Lafuente, Laura
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Sanz, Ana Belén
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Ruiz Ortega, Marta
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Ortiz Arduán, Alberto
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Sánchez Niño, María Dolores
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