Dataset Information

Circulating microRNAs, potential biomarkers for drug-induced liver injury.

ABSTRACT: Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for approximately 30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose- and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.

SUBMITTER: Wang K

PROVIDER: S-EPMC2657429 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Circulating microRNAs, potential biomarkers for drug-induced liver injury.

Wang Kai K Zhang Shile S Marzolf Bruz B Troisch Pamela P Brightman Amy A Hu Zhiyuan Z Hood Leroy E LE Galas David J DJ

Proceedings of the National Academy of Sciences of the United States of America 20090225 11

Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been a ...[more]

PMID: 19246379

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Project description:Purpose microRNAs (miRs) are crucial intracellular mediators of various biological processes, also affecting the cardiovascular system. Recently, it has been shown that miRs circulate extracellularly in the bloodstream and that such circulating miRs change in response to physical activity. Therefore, the purpose of the current study was to investigate heart/muscle specific and inflammation related miRs in plasma of individuals before, directly after, and 24 h after a marathon run and to analyze their relation to conventional biochemical, cardiovascular, and performance indexes. Male endurance athletes (n =14) were recruited for the study after performing a battery of cardiac functional tests. Blood samples were collected before, directly after, and 24 h after a public marathon run. miR-1, miR-133, miR-206, miR-499, miR-208b, miR-21, and miR-155 were measured using individual Taqman assays and normalized to Caenorhabditis elegans miR-39 (cel-39) spike-in control. Moreover, soluble cardiac, inflammatory, and muscle damage markers were determined. As a result, skeletal- and heart muscle-specific miRs showed a significant increase after the marathon. The strongest increase was observed for miR-206. Twenty-four hours after the run, only miR-499 and miR-208b were returned to preexercise levels, whereas the others were still enhanced. In contrast, miR-21 and -155 were not affected by exercise. miR-1, -133a, and -206 correlated to aerobic performance parameters such as maximum oxygen uptake (VO(2max)) and running speed at individual anaerobic lactate threshold (VIAS). miR-1 showed a moderate negative correlation with fractional shortening, whereas miR-133a was positively related to the thickness of intraventricular septum. None of the miRs correlated with cardiac injury markers such as troponin T, troponin I, and pro-brain natriuretic peptide. In conclusion, these findings suggest a potential role for muscle- and heart-specific miRs in cardiovascular adaptation processes after endurance exercise. Moreover, the specific correlation of miR-1, -133a, and -206 to performance parameters indicated their potential role as biomarkers of aerobic capacity.

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Circulating microRNAs, potential biomarkers for drug-induced liver injury.

Publications

Circulating microRNAs, potential biomarkers for drug-induced liver injury.

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