Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury
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Tartalom: http://dx.doi.org/10.1073/pnas.0406421101
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published

Type = Article
Cím:
Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury
Létrehozó:
Hamar, Péter
Song, E.
Kökény, Gábor
Chen, A.
Ouyang, N.
Liebermann, J.
Kiadó:
National Academy of Sciences
Dátum:
2004-10-12
Téma:
QR180 Immunology / immunológia
Tartalmi leírás:
Fas-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.
Típus:
Article
PeerReviewed
Formátum:
application/pdf
Azonosító:
Hamar, Péter and Song, E. and Kökény, Gábor and Chen, A. and Ouyang, N. and Liebermann, J. (2004) Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. Proceedings of the National Academy of Sciences, 101 (41). pp. 14883-14888. ISSN 0027-8424
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