Hamar, PéterSong, ErweiKökény, GaborChen, AllenOuyang, NengtaiLieberman, Judy2019-10-052004Hamar, P., E. Song, G. Kokeny, A. Chen, N. Ouyang, and J. Lieberman. 2004. “Small Interfering RNA Targeting Fas Protects Mice against Renal Ischemia-Reperfusion Injury.” Proceedings of the National Academy of Sciences 101 (41): 14883–88. https://doi.org/10.1073/pnas.0406421101.0027-84240744-28311091-6490http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483383Fas-mediated apoptosis has been suggested to contribute to tubular cell death after renal ischemia-reperfusion injury. Here we investigate whether small interfering RNA (siRNA) duplexes targeting Fas protect mice from acute renal failure after clamping of the renal artery. Renal ischemia-reperfusion injury was induced by clamping the renal vein and artery for 15 or 35 min. Mice were treated before or after ischemia with siRNA targeting Fas or a control gene, administered by hydrodynamic injection, low-volume renal vein injection, or both. Treated mice were evaluated for renal Fas protein and mRNA expression, tissue histopathology, and apoptosis by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. Blood urea nitrogen and survival were monitored in mice in which the contralateral kidney had been removed. A single hydrodynamic injection of Fas siRNA reduced Fas mRNA and protein expression in the kidney 4-fold. Kidneys from mice that received Fas siRNA two days earlier had substantially less renal tubular apoptosis by TUNEL staining and less tubular atrophy and hyaline damage. Whereas 90% of mice pretreated with saline or GFP siRNA died, only 20% of Fas-siRNA-pretreated animals died. The same survival advantage was provided by a single low-volume Fas siRNA injection into the renal vein. Moreover, postischemic injection through the renal vein protected 38% of mice from death. This study confirms the importance of Fas-mediated apoptosis in renal ischemia-reperfusion injury. Silencing Fas by systemic or local catheterization holds therapeutic promise to limit ischemia-reperfusion injury.en-USJournal Article2019-10-0510.1073/pnas.0406421101