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.


CONCLUSIONS
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.
Department of Surgery, University of Western Ontario, London, Ontario, Canada.
Biao
B
Feng
Gang
G
Chen
Xiufen
X
Zheng
Hongtao
H
Sun
Xusheng
X
Zhang
Zhu-Xu
ZX
Zhang
Ying
Y
Xiang
Thomas E
TE
Ichim
Bertha
B
Garcia
Patrick
P
Luke
Anthony M
AM
Jevnikar
Wei-Ping
WP
Min
D000818:Animals; D017931:DNA Primers; D020868:Gene Silencing; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009195:Peroxidase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use*; D012079:Renal Circulation / Q000502:physiology*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051841:Transcription Factor RelB / Q000235:genetics*
D017931:DNA Primers; D034741:RNA, Small Interfering; C497594:Relb protein, mouse; D051841:Transcription Factor RelB; D009195:Peroxidase