Revealing the mechanism of Fructus meliae toosendan-induced liver injury in mice by integrating microRNA and mRNA-based toxicogenomics data
Revealing the mechanism of Fructus meliae toosendan-induced liver injury in mice by integrating microRNA and mRNA-based toxicogenomics data
复制标题
整合microRNA和mRNA毒理组学数据揭示川楝子诱导小鼠肝损伤的机制
DOI：
10.1039/c5ra10112c
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发表时间：
2015-01-01
期刊：
影响因子：
3.9
通讯作者：
Gao, Yue
中科院分区：
文献类型：
--
作者：
Ji, Cai;Zheng, Jie;Gao, Yue
川楝子（Fructus Meliae Toosendan，FMT）是我国著名的杀虫、药用植物。以往的一些研究表明，它可以诱导肝毒性，但其潜在的毒性成分及其诱导肝毒性的机制尚未完全研究。在本研究中，我们进行了一种方法，整合的数据从microRNA（miRNA）和mRNA的表达谱结合一般毒理学评估方法来研究FMT诱导的肝损伤（FMT-ILI）在小鼠。染毒9天后，观察小鼠体重、血清生化指标和组织病理学变化。在FMT处理的小鼠的肝脏中，总共有37个miRNAs和931个mRNAs差异表达。通过miRNA靶标筛选和数据交叉，共获得115个已鉴定miRNA的mRNA靶标。基因通路分析表明，脂代谢紊乱在FMT-ILI中起重要作用。多方面的基因组分析结果为FMT-ILI的机制提供了新的见解，有助于更好地理解中药肝毒性的肝脏病理生物学。
Fructus Meliae Toosendan (FMT, ChuanLianZi in Chinese) is recognized as an insecticidal and medicinal plant in China. A few previous studies demonstrated that it can induce hepatotoxicity, however, its potential toxic compositions and their mechanism of the induction of hepatotoxicity has not been completely investigated. In the present study, we performed an approach for integrating the data from microRNA (miRNA) and mRNA expression profiles combined with the general toxicological assessments method to investigate FMT-induced liver injury (FMT-ILI) in mice. Changes in the body weight, serum biochemical parameters, and histopathology were observed after 9 days exposure to FMT. A total of 37 miRNAs and 931 mRNAs were differentially expressed in the liver of FMT-treated mice. By miRNA target filter and data intersection, a total of 115 mRNA targets of the identified miRNA were obtained. Ingeniuty pathway analysis showed that lipid metabolism disorders play critical roles in FMT-ILI. Results from multi-facets of the genomic profiling provided novel insights into the mechanisms of FMT-ILI and contributed to a better understanding of liver pathobiology of Traditional Chinese Medicine (TCM) hepatoxicity.