Plasma MicroRNAs as Sensitive and Specific Biomarkers of Tissue Injury

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2009-11, Vol.55 (11), p.1977-1983
• Main Authors: Laterza, Omar F, Lim, Lee, Garrett-Engele, Philip W, Vlasakova, Katerina, Muniappa, Nagaraja, Tanaka, Wesley K, Johnson, Jason M, Sina, Joseph F, Fare, Thomas L, Sistare, Frank D, Glaab, Warren E
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Animals; Aqueous solutions; Biological and medical sciences; Biomarkers; Biomarkers - blood; Brain damage; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Heart Injuries - diagnosis; Heart Injuries - genetics; Investigative techniques, diagnostic techniques (general aspects); Kidney - injuries; Kidney - pathology; Liver; Liver - injuries; Liver - pathology; Male; Medical sciences; MicroRNAs - blood; Molecular biophysics; Muscle, Skeletal - injuries; Muscle, Skeletal - pathology; Myocardium - pathology; Plasma; Rats; Rats, Sprague-Dawley; Rodents; Stroke - diagnosis; Stroke - genetics; Tissues; Toxicants; Toxicity; Wounds and Injuries - diagnosis; Wounds and Injuries - genetics
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2009.131797

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