NF-κB-dependent genes induced by proteinuria and identified using DNA microarrays

    loading  Checking for direct PDF access through Ovid


BackgroundA close correlation has been shown between tubulointerstitial (TI) injury and the outcome of renal dysfunction, and nuclear factor-kappaB (NFκB) has been shown to play a key role in proteinuria-induced TI injury. To explore the molecular mechanisms of the proteinuria-induced TI injury further, we have analyzed renal gene expression with DNA microarrays, with and without specific inhibition of NF-κB in the proximal tubules.MethodsUnilaterally nephrectomized rats loaded with bovine serum albumin (BSA) were used as a model of proteinuric renal injury. Renal NF-κB activation was inhibited by gene transfer of the truncated form of IκBα (inhibitor of NF-κB) via the injection of a recombinant adenovirus vector into the renal artery, an method established in a previous study. Total RNA was extracted from the kidney and analyzed with a DNA microarrays containing 1081 genes.ResultsRenal NF-κB activation and TI injury in BSA-loaded proteinuric rats were inhibited by the gene transfer of the truncated form of IκBα. DNA microarray analysis revealed 45 up-regulated genes and six down-regulated genes in the proteinuric rats, and expression of 23 of these 51 genes was significantly altered by NF-κB inhibition. Among these 23 genes, we focused on clusterin and confirmed the results of microarray analysis by Western blotting and PCR.ConclusionIn this study, 23 genes of 51 proteinuria-related genes were regulated by NF-κB activation, suggesting that some of these genes may serve as target molecules for the treatment of progressive TI injury.

    loading  Loading Related Articles