Circulating microRNAs, potential biomarkers for drug-induced liver injury
Circulating microRNAs, potential biomarkers for drug-induced liver injury
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DOI：
10.1073/pnas.0813371106
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发表时间：
2009-03-17
影响因子：
11.1
通讯作者：
Galas, David J.
中科院分区：
文献类型：
--
作者：
Wang, Kai;Zhang, Shile;Galas, David J.
药物性肝损伤是许多药物常见的副作用，对患者健康构成重大威胁，并对医疗保健支出产生巨大的经济影响。人们已经做出了许多努力来确定可靠的预测标记，以检测药物引起的肝脏损伤的早期迹象，肝脏是体内最脆弱的器官之一。然而，这些研究并没有提供比已有近 30 年历史的血清转氨酶标记物更多的信息。使用对乙酰氨基酚过量引起的小鼠肝损伤作为模型系统，我们观察到对照动物和过量动物之间肝组织和血浆中 microRNA 的谱和水平存在高度显着差异。根据我们对正常组织中 microRNA 表达的调查，一些 microRNA（如信使 RNA）显示出有限的组织分布。从过量服用对乙酰氨基酚的动物身上收集的血浆中，许多循环 microRNA 升高，并在肝脏中高表达。我们已经证明，特定的 microRNA 种类，如 mir-122 和 mir-192，都在肝组织中富集，并在血浆中表现出剂量和暴露时间依赖性变化，与血清转氨酶水平和肝变性的组织病理学平行，但它们的变化可以显着更早地检测到。这些发现表明，使用特定的循环 microRNA 作为药物引起的肝损伤的敏感且信息丰富的生物标志物具有潜力。
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 approximate to 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.