Integrated analysis of microRNA and mRNA expression profiles highlights the complex and dynamic behavior of toosendanin-induced liver injury in mice.
Integrated analysis of microRNA and mRNA expression profiles highlights the complex and dynamic behavior of toosendanin-induced liver injury in mice.
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microRNA 和 mRNA 表达谱的综合分析凸显了川楝素诱导的小鼠肝损伤的复杂和动态行为
DOI：
10.1038/srep34225
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发表时间：
2016-10-05
影响因子：
4.6
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Lu X;Ji C;Tong W;Lian X;Wu Y;Fan X;Gao Y
川楝素具有丰富的药理作用和农业开发价值。然而，TSN或含有TSN的楝科植物在传统中药中引起的肝毒性已被报道，TSN诱导的肝损伤（TILI）的机制仍然在很大程度上未知。在这项研究中，TSN对小鼠肝脏的剂量和时间依赖性影响进行了研究，通过整合microRNA-mRNA方法以及一般毒理学评估。结果发现，剂量和时间依赖性的肝损伤和整体microRNA和mRNA表达的变化。特别是，9天80 mg/kg TSN暴露导致小鼠最严重的肝损伤，并且在21天80 mg/kg TSN给药后意外观察到对TILI的肝适应。基于预测的差异表达microRNA靶点与3个时间点差异表达mRNAs的交叉通路分析，提示TILI可能是由谷胱甘肽耗竭、线粒体功能障碍和脂质代谢异常引起，最终导致肝细胞坏死，而肝再生可能在肝脏对TILI的适应中起重要作用。我们的研究结果表明，整合microRNA-mRNA的方法可以为TILI的复杂和动态行为提供新的见解。
Triterpenoid Toosendanin (TSN) exhibits a plenty of pharmacological effects in human and great values in agriculture. However, the hepatotoxicity caused by TSN or Melia-family plants containing TSN used in traditional Chinese medicine has been reported and the mechanisms of TSN-induced liver injury (TILI) still remain largely unknown. In this study, the dose- and time-dependent effects of TSN on mice liver were investigated by an integrated microRNA-mRNA approach as well as the general toxicological assessments. As the results, the dose- and time-dependent liver injury and alterations in global microRNA and mRNA expressions were detected. Particularly, 9-days 80 mg/kg TSN exposure caused most serious liver injury in mice and the hepatic adaptation to TILI was unexpectedly observed after 21-days 80 mg/kg TSN administration. Based on the pathway analysis of the intersections between predicted targets of differentially expressed microRNAs and differentially expressed mRNAs at three time points, it revealed that TILI may be caused by glutathione depletion, mitochondrial dysfunction and lipid dysmetabolism, ultimately leading to hepatocytes necrosis in liver, while liver regeneration may play an important role in the hepatic adaptation to TILI. Our results demonstrated that the integrated microRNA−mRNA approach could provide new insight into the complex and dynamic behavior of TILI.
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影响因子：
3.8
作者：
Celius T;Pansoy A;Matthews J;Okey AB;Henderson MC;Krueger SK;Williams DE
通讯作者：
Williams DE
影响因子：
13.5
作者：
Inoue, Y;Tomiya, T;Fujiwara, K
通讯作者：
Fujiwara, K
影响因子：
4.1
作者：
Lizarraga, Daneida;Gaj, Stan;van Delft, Joost H. M.
通讯作者：
van Delft, Joost H. M.
影响因子：
3.9
作者：
Celius, Trine;Roblin, Steven;Okey, Allan B.
通讯作者：
Okey, Allan B.
DOI：
10.1016/j.bbrc.2011.05.127
发表时间：
2011-06-24
影响因子：
3.1
作者：
Abdel-Bakky, Mohamed Sadek;Hammad, Mohamed A.;Ashfaq, Mohammad K.
通讯作者：
Ashfaq, Mohammad K.