Small interfering RNA targeting RelB protects against renal ischemia-reperfusion injury.

BACKGROUND: Nuclear factor kappaB (NF-kappaB) has been found to be critical to the pathogenesis of renal ischemia-reperfusion injury (IRI). Using small interfering RNA (siRNA) to silence the expression of RelB, a component of the transcription factors Rel/nuclear factor kappaB, may protect renal IRI. Here, we report an siRNA-based treatment of preventing IRI.

METHODS: Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. The therapeutic effects of siRNA were evaluated in renal function, histologic examination, and overall survival after lethal IRI.

RESULTS: A single injection of RelB siRNA resulted in knockdown of renal RelB expression. In comparison with control mice, levels of blood urea nitrogen and serum creatinine were significantly decreased in mice treated with siRNA. Pathologic examination demonstrated that tissue injury caused by IRI was markedly reduced as a result of RelB siRNA treatment. Additionally, with RelB siRNA treatment, immunohistochemistry showed a significant attenuation of tumor necrosis factor-alpha expression. Furthermore, survival experiments revealed that more than 90% of control mice died from lethal IRI, whereas 80% of siRNA-pretreated mice survived until the end of the 8-day observation period.

CONCLUSION: Silencing RelB, using siRNA, can significantly attenuate IRI-induced renal dysfunction and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy.