遗传 ›› 2022, Vol. 44 ›› Issue (6): 501-509.doi: 10.16288/j.yczz.22-069

• 研究报告 • 上一篇    下一篇

通过时间基因表达谱分析探究异烟肼引起肝损伤的机制

田子钊(), 周晨希, 周伟, 李沫, 褚云鹏, 怀聪(), 秦胜营()   

  1. 上海交通大学Bio-X研究院,上海 200030
  • 收稿日期:2022-03-10 修回日期:2022-04-26 出版日期:2022-06-20 发布日期:2022-05-11
  • 通讯作者: 怀聪,秦胜营 E-mail:tianzizhao@sjtu.edu.cn;huaic@sjtu.edu.cn;chinsir@sjtu.edu.cn
  • 作者简介:田子钊,在读硕士研究生,专业方向:生物学。E-mail: tianzizhao@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金项目资助编号(81773818);国家自然科学基金项目资助编号(82003856)

Analysis of time-series gene expression data to explore mechanisms of isoniazid-induced liver toxicity

Tian Zizhao(), Zhou Chenxi, Zhou Wei, Li Mo, Chu Yunpeng, Huai Cong(), Qin Shengying()   

  1. Bio-X Institute, Shanghai Jiaotong University, Shanghai 200030, China
  • Received:2022-03-10 Revised:2022-04-26 Online:2022-06-20 Published:2022-05-11
  • Contact: Huai Cong,Qin Shengying E-mail:tianzizhao@sjtu.edu.cn;huaic@sjtu.edu.cn;chinsir@sjtu.edu.cn
  • Supported by:
    Supported by the National Nature Science Foundation of China Nos(81773818);Supported by the National Nature Science Foundation of China Nos(82003856)

摘要:

抗结核药物异烟肼具有肝脏毒性,其发生机制需要进一步阐明。本研究使用异烟肼处理肝细胞,分析不同处理时间表达谱的差异。通过对差异表达基因进行聚类分析和功能富集分析,共得到6个与肝脏毒性相关的基因簇和一系列相关通路;进一步通过蛋白互作分析和时间序列差异分析方法,筛选出表达水平具有时间依赖性的13个关键基因。本研究结果为理解异烟肼引发肝脏毒性过程提供了思路,为今后药物性肝脏毒性的监测以及治疗提供了新的靶基因。

关键词: 异烟肼, 肝细胞, 肝脏毒性, 时间序列分析

Abstract:

Isoniazid (INH) is a first-line anti-tuberculosis drug which can cause idiosyncratic liver injury, while the underlying mechanisms need to be further elucidated. In this study, we explored the time series gene expression profiling of a hepatocyte cell line under isoniazid treatment. Through cluster analysis and enrichment analysis of differentially expressed genes, we revealed a total of 6 gene clusters and a series of pathways related to hepatotoxicity, and 13 key candidate genes were identified according to the protein-protein interaction (PPI) network analysis and maSigPro analysis. These findings lay a foundation for understanding the mechanisms of isoniazid -induced liver toxicity and provide new target genes for the monitoring and treatment of INH-induced hepatotoxicity in the future.

Key words: isoniazid, hepatocytes, liver toxicity, time series analysis