Transcriptional regulation of NF-κB by ring type decoy oligodeoxynucleotide in an animal model of nephropathy

Inflammation of the tubulointerstitial compartment, leading to fibrosis, is a major factor in the progressive loss of renal function in a wide variety of kidney diseases. In order to develop a therapeutic approach for nephropathy, we examined the simultaneous inhibition of transcription factor nuclear factor-κB (NF-κB), which is responsible for a wide range of cellular processes, especially inflammation, in a mouse model of unilateral ureteral obstruction. In this study, we employed a ring-type NF-κB (R-NF-κB) decoy oligodeoxynucleotide (ODN), containing consensus promoter sequences of NF-κB. This R-NF-κB decoy ODN is more highly resistant to degradation by nucleases than is the current phosphothiolated double stranded NF-κB decoy ODN. The inhibitory effect of R-NF-κB decoy ODN on nephropathy was confirmed by molecular and histological examinations. In addition, treatment with R-NF-κB decoy ODN reduced the activities of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Interestingly, the treatment with R-NF-κB decoy ODN also suppressed the gene expression of transforming growth factor-β1 and fibronectin, resulting in the inhibition of fibrotic changes. These results suggest that the inhibition of NF-κB using R-NF-κB decoy ODN has potential therapeutic application in the prevention of renal fibrosis.