Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury

P. Hamar, Erwei Song, Gabor Kökeny, Allen Chen, Nengtai Ouyang, Judy Lieberman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)14883-14888
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number41
DOIs
Publication statusPublished - Oct 12 2004

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Reperfusion Injury
Small Interfering RNA
Kidney
Renal Veins
Injections
Apoptosis
In Situ Nick-End Labeling
Renal Artery
Hydrodynamics
Constriction
Staining and Labeling
Messenger RNA
Hyalin
DNA Nucleotidylexotransferase
Blood Urea Nitrogen
Acute Kidney Injury
Catheterization
Atrophy
Proteins
Cell Death

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. / Hamar, P.; Song, Erwei; Kökeny, Gabor; Chen, Allen; Ouyang, Nengtai; Lieberman, Judy.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 41, 12.10.2004, p. 14883-14888.

Research output: Contribution to journalArticle

Hamar, P. ; Song, Erwei ; Kökeny, Gabor ; Chen, Allen ; Ouyang, Nengtai ; Lieberman, Judy. / Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 41. pp. 14883-14888.
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