Inhibition of nuclear factor-kappa B (NF-κB) activation attenuates ureteric damage in obstructive uropathy

ObjectiveNuclear factor (NF)-κB is a ubiquitous transcription factor that can be activated by multiple signals. To elucidate the role of NF-KB and the effects of NF-κB inhibitor on ureteric damages in obstructive uropathy, we conducted this study.MethodsThe expressions of NF-κBp50, NF-κBp65, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), proliferation cell nuclear antigen (PCNA) and cell apoptosis were examined in 80 rats. Pyrrolidine dithiocarbamate (PDTC) was administered to 40 rats. The others served as controls.ResultsAfter ureteric ligation, hydroureter and ureteric damages progressively aggravated. But the severity of hydroureter and fibrosis of muscle layer in the ligated ureters in the treated group were significantly milder than those of the control group. The expressions of NF-κBp50 and NFκ-Bp65 in the smooth muscle layer of obstructed ureters were found in the rats in control group from the day 14 after ureteric ligation. The expressions of NF-κBp65 and NF-κBp50 in the nuclei of muscle cells in obstructed ureters were correlated significantly with the expressions of IL-6, TNF-α, PCNA and the number of the apoptotic cells. The expressions of NF-κBp50, NF-κBp65 in the nuclei of myocytes and fibrotic changes of smooth muscle layer were correlated significantly. Treatment with PDTC diminished the expressions of NF-κBp50 and NF-κBp65. The expression of IL-6, TNF-α, PCNA and the labeling index of apoptotic cells in the smooth muscle layer of ligated ureters in the PDTC-treated group were also decreased.ConclusionsWe concluded that expression of NF-κB might contribute to the ureteric damage in obstructive uropathy, and that inhibition of NF-kB could attenuate the tissue damages of obstructed ureters.