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Clinical Chemistry 55: 1977-1983, 2009. First published September 10, 2009; 10.1373/clinchem.2009.131797
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(Clinical Chemistry. 2009;55:1977-1983.)
© 2009 American Association for Clinical Chemistry, Inc.

Molecular Diagnostics and Genetics

Plasma MicroRNAs as Sensitive and Specific Biomarkers of Tissue Injury

Omar F. Laterza1, Lee Lim2, Philip W. Garrett-Engele3, Katerina Vlasakova4, Nagaraja Muniappa4, Wesley K. Tanaka1, Jason M. Johnson3, Joseph F. Sina4, Thomas L. Fare5, Frank D. Sistare4 and Warren E. Glaab4,a

1 Merck Research Laboratories, Clinical Development Laboratory, Rahway, NJ; 2 Sirna Therapeutics, San Francisco, CA; 3 Merck Research Laboratories, Molecular Profiling and Research Informatics, Boston, MA; Merck Research Laboratories, 4 Safety Assessment and 5 External Scientific Affairs, West Point, PA.

aAddress correspondence to this author at: Merck Research Laboratories, Safety Assessment, WP45-320, West Point, PA 19486. Fax +215-652-4944; e-mail warren_glaab{at}merck.com.

Background: MicroRNAs (miRNAs) are endogenous, small noncoding RNAs. Because of their size, abundance, tissue specificity, and relative stability in plasma, miRNAs hold promise as unique accessible biomarkers to monitor tissue injury.

Methods: We investigated the use of liver-, muscle- and brain-specific miRNAs as circulating biomarkers of tissue injury. We used a highly sensitive quantitative PCR assay to measure specific miRNAs (miR-122, miR-133a, and miR-124) in plasma samples from rats treated with liver or muscle toxicants and from a rat surgical model of stroke.

Results: We observed increases in plasma concentrations of miR-122, miR-133a, and miR-124 corresponding to injuries in liver, muscle, and brain, respectively. miR-122 and miR-133a illustrated specificity for liver and muscle toxicity, respectively, because they were not detectable in the plasma of animals with toxicity to the other organ. This result contrasted with the results for alanine aminotransferase (ALT) and aspartate aminotransferase, which were both increased with either organ toxicity. Furthermore, miR-122 exhibited a diagnostic sensitivity superior to that of ALT when the results were correlated to the liver histopathologic results. The miR-124 concentration increased in the plasma of rats 8 h after surgery to produce brain injury and peaked at 24 h, while the miR-122 and miR-133a concentrations remained at baseline values.

Conclusions: These results demonstrate that tissue-specific miRNAs may serve as diagnostically sensitive plasma biomarkers of tissue injury.






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Copyright © 2009 by the American Association for Clinical Chemistry.