Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice

doi:10.1016/j.toxlet.2020.08.007

	Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice
	Zhao, Jie 1,2,3,4; Xie, Cen 4,6; Wang, Kanglong 6; Takahashi, Shogo 4; Krausz, Kristopher W.4; Lu, Dasheng 4; Wang, Qiong 4; Luo, Yuhong 4; Gong, Xianqiong 4; Mu, Xiyan 3
刊名	TOXICOLOGY LETTERS
	2020-10-15
卷号	333 页码:290-302
关键词	Triptolide Transcriptomics Metabolomics Apoptosis Acylcarnitine
ISSN号	0378-4274
DOI	10.1016/j.toxlet.2020.08.007
通讯作者	Wang, Qiao(qiaowang88@hotmail.com) ; Su, Suwen(suswmk@hebmu.edu.cn)
英文摘要	Triptolide, a major active component of Triptergium wilfordii Hook. f, is used in the treatment of autoimmune disease. However, triptolide is associated with severe adverse reactions, especially hepatotoxicity, which limits its clinical application. To examine the underlying mechanism of triptolide-induced liver injury, a combination of dose- and time-dependent toxic effects, RNA-seq and metabolomics were employed. Triptolide-induced toxicity occurred in a dose- and time-dependent manners and was characterized by apoptosis and not necroptosis. Transcriptomics profiles of the dose-dependent response to triptolide suggested that PI3K/AKT, MAPK, TNF alpha and p53 signaling pathways were the vital steps in triptolide-induced hepatocyte apoptosis. Metabolomics further revealed that glycerophospholipid, fatty acid, leukotriene, purine and pyrimidine metabolism were the major metabolic alterations after triptolide exposure. Finally, acylcarnitines were identified as potential biomarkers for the early detection of triptolide-induced liver injury.
资助项目	National Cancer Institute Intramural Research Program, Hebei Science and Technology Department in China[17392501D] ; National Science Foundation of China[81973469] ; Doctoral Scientific Research Start-up Foundation from Henan University of Chinese Medicine[RSBSJJ2018-13]
WOS关键词	INDUCED HEPATOTOXICITY ; ACETAMINOPHEN TOXICITY ; PATHWAY ; ACYLCARNITINES ; INHIBITION ; MECHANISMS ; APOPTOSIS ; PI3K/AKT ; RATS
WOS研究方向	Toxicology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000579907000031
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291376]
专题	中国科学院上海药物研究所
通讯作者	Wang, Qiao; Su, Suwen
作者单位	1.Henan Univ Chinese Med, Acad Chinses Med Sci, Chinese Med Dev Henan Prov, Zhengsshou, Henan, Peoples R China 2.Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Collaborat Innovat Ctr Resp Dis Diag & Treatment, Zhengzhou, Henan, Peoples R China 3.Hebei Med Univ, Sch Pharmaceut Sci, Shijiazhuang, Hebei, Peoples R China 4.NCI, Lab Metab, Bethesda, MD USA 5.Hebei Med Univ, Dept Pharmacol, Shijiazhuang, Hebei, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Jie,Xie, Cen,Wang, Kanglong,et al. Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice[J]. TOXICOLOGY LETTERS,2020,333:290-302.
APA	Zhao, Jie.,Xie, Cen.,Wang, Kanglong.,Takahashi, Shogo.,Krausz, Kristopher W..,...&Gonzalez, Frank J..(2020).Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice.TOXICOLOGY LETTERS,333,290-302.
MLA	Zhao, Jie,et al."Comprehensive analysis of transcriptomics and metabolomics to understand triptolide-induced liver injury in mice".TOXICOLOGY LETTERS 333(2020):290-302.