2024-03-29T02:28:49Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/973262017-11-28T13:36:37Zcom_10261_22com_10261_1col_10261_275
DIGITAL.CSIC
author
Ucero, Alvaro C.
author
Benito-Martin, Alberto
author
Santamaria, Beatriz
author
Ruiz-Ortega, Marta
author
Ortiz, Alberto
2014-05-27T12:58:38Z
2014-05-27T12:58:38Z
2014
BBA - Molecular Basis of Disease 1842(2): 293-303 (2014)
http://hdl.handle.net/10261/97326
10.1016/j.bbadis.2013.11.022
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.
eng
openAccess
Apoptosis
Inflammation
Kidney
NAMPT
Diabetes
Endogenous NAMPT dampens chemokine expression and apoptotic responses in stressed tubular cells
artículo
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https://digital.csic.es/bitstream/10261/97326/4/Endogenous%20NAMPT%20dampens.pdf
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https://digital.csic.es/bitstream/10261/97326/6/Endogenous%20NAMPT%20dampens.pdf.txt
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Endogenous NAMPT dampens.pdf.txt