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| Título: | Endogenous NAMPT dampens chemokine expression and apoptotic responses in stressed tubular cells |
Autor: | Ucero, Alvaro C.; Benito-Martin, Alberto; Santamaria, Beatriz CSIC ORCID; Ruiz-Ortega, Marta; Ortiz, Alberto | Palabras clave: | Apoptosis Inflammation Kidney NAMPT Diabetes |
Fecha de publicación: | 2014 | Editor: | Elsevier | Citación: | BBA - Molecular Basis of Disease 1842(2): 293-303 (2014) | Resumen: | Diabetic nephropathy (DN) is the most common cause of end-stage renal disease and identification of new therapeutic targets is needed. Nicotinamide phosphoribosyltransferase (NAMPT) is both an extracellular and intracellular protein. Circulating NAMPT is increased in diabetics and in chronic kidney disease patients. The role of NAMPT in renal cell biology is poorly understood. NAMPT mRNA and protein were increased in the kidneys of rats with streptozotocin-induced diabetes. Immunohistochemistry localized NAMPT to glomerular and tubular cells in diabetic rats. The inflammatory cytokine TNFα increased NAMPT mRNA, protein and NAD production in cultured kidney human tubular cells. Exogenous NAMPT increased the mRNA expression of chemokines MCP-1 and RANTES. The NAMPT enzymatic activity inhibitor FK866 prevented these effects. By contrast, FK866 boosted TNFα-induced expression of MCP-1 and RANTES mRNA and endogenous NAMPT targeting by siRNA also had a proinflammatory effect. Furthermore, FK866 promoted tubular cell apoptosis in an inflammatory milieu containing the cytokines TNFα/IFNγ. In an inflammatory environment FK866 promoted tubular cell expression of the lethal cytokine TRAIL. These data are consistent with a role of endogenous NAMPT activity as an adaptive, protective response to an inflammatory milieu that differs from the proinflammatory activity of exogenous NAMPT. Thus, disruption of endogenous NAMPT function in stressed cells promotes tubular cell death and chemokine expression. This information may be relevant for the design of novel therapeutic strategies in DN. © 2013. | Descripción: | et al. | Versión del editor: | http://dx.doi.org/10.1016/j.bbadis.2013.11.022 | URI: | http://hdl.handle.net/10261/97326 | DOI: | 10.1016/j.bbadis.2013.11.022 | Identificadores: | doi: 10.1016/j.bbadis.2013.11.022 issn: 0925-4439 |
| Aparece en las colecciones: | (IIBM) Artículos |
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| Endogenous NAMPT dampens.pdf | 278,43 kB | Adobe PDF |  Visualizar/Abrir |
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