Journal Article

NF-κB activation and overexpression of regulated genes in human diabetic nephropathy

Sergio Mezzano, Claudio Aros, Alejandra Droguett, M. Eugenia Burgos, Leopoldo Ardiles, Claudio Flores, Herman Schneider, Marta Ruiz-Ortega and Jesús Egido

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 19, issue 10, pages 2505-2512
Published in print October 2004 | ISSN: 0931-0509
Published online July 2004 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfh207
NF-κB activation and overexpression of regulated genes in human diabetic nephropathy

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Background. Nuclear factor-κB (NF-κB) regulates genes involved in renal disease progression, such as the chemokines monocyte chemoattractant protein-1 (MCP-1) and RANTES. NF-κB is activated in experimental models of renal injury, and in vitro studies also suggest that proteinuria and angiotensin II could be important NF-κB activators. It has been proposed that locally produced MCP-1 may be involved in the development of diabetic nephropathy (DN). We examined the hypothesis that NF-κB could be an indicator of renal damage progression in DN.

Methods. Biopsy specimens from 11 patients with type 2 diabeties and overt nephropathy were studied by southwestern histochemistry for the in situ detection of activated NF-κB. In addition, by immunohistochemistry and/or in situ hybridization, we studied the expression of MCP-1 and RANTES, whose genes are regulated by NF-κB.

Results. NF-κB was detected mainly in cortical tubular epithelial cells and, to a lesser extent, in some glomerular and interstitial cells. A strong upregulation of MCP-1 and RANTES was observed in all the cases, mainly in tubular cells, and there was a strong correlation between the expression of these chemokines and NF-κB activation in the same cells, as observed in serial sections (r = 0.7; P = 0.01). In addition, the tubular expression of these chemokines was correlated mainly with the magnitude of the proteinuria (P = 0.002) and with interstitial cell infiltration (P<0.05).

Conclusions. The activation of NF-κB and the transcription of certain pro-inflammatory chemokines in tubular epithelial cells are markers of progressive DN. Proteinuria might be one of the main factors inducing the observed pro-inflammatory phenotype.

Keywords: diabetic nephropathy; MCP-1; NF-κB; RANTES; renal disease progression

Journal Article.  4224 words.  Illustrated.

Subjects: Nephrology

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