Journal
FEBS LETTERS
Volume 585, Issue 15, Pages 2488-2492Publisher
WILEY
DOI: 10.1016/j.febslet.2011.06.032
Keywords
Autoregulation; Inducible nitric oxide synthase; RNA interference; Short hairpin RNA
Funding
- International Anesthesia Research Society, Cleveland, OH
- National Institutes of Health, Bethesda, MD [R01 GM065211]
- American Heart Association Mid-Atlantic Affiliate, Baltimore, MD [10GRNT3900019]
- University of Virginia, Charlottesville, VA
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Vector-mediated delivery of short-hairpin RNA (shRNA) to regulate gene expression holds a great therapeutic promise. We hypothesize that gene expression can be autoregulated with RNA interference. We used inducible nitric oxide synthase (iNOS) as a gene model to test this hypothesis. Lipopolysaccharide dose-dependently increased iNOS in rat aortic smooth muscle cells and the nitrite production from these cells. These increases were attenuated in cells transfected with plasmids containing code for iNOS shRNA whose expression was controlled by an iNOS promoter. The production of shRNA was lipopolysaccharide dose-dependent. The lipopolysaccharide-induced iNOS expression in rat C6 glioma cells also was attenuated by transfection with plasmids containing the iNOS shRNA code. These results provide proof-of-concept evidence for using RNA interference technique to achieve autoregulation of gene expression. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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