Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice

Guo, Qiuyan1,2; Wu, Jiangpeng3,4,5; Wang, Qixin1,2; Huang, Yuwen6; Chen, Lin1,2; Gong, Jie7,8; Du, Maobo9; Cheng, Guangqing1,2; Lu, Tianming1,2; Zhao, Minghong1,2; Zhao, Yuan; Qiu, Chong1,2; Xia, Fei1,2; Zhang, Junzhe1,2; Chen, Jiayun1,2; Qiu, Feng3,4; Wang, Jigang1,2,3,4,5

2023-08-01

10.1016/j.jpha.2023.03.004

JOURNAL OF PHARMACEUTICAL ANALYSIS   Impact Factor & Quartile

2095-1779

2214-0883

Tripterygium glycosides tablet (TGT), the classical commercial drug of Tripterygium wilfordii Hook. F. has been effectively used in the treatment of rheumatoid arthritis, nephrotic syndrome, leprosy, Behcet's syndrome, leprosy reaction and autoimmune hepatitis. However, due to its narrow and limited treatment window, TGT-induced organ toxicity (among which liver injury accounts for about 40% of clinical reports) has gained increasing attention. The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing (scRNA-seq) technology. The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin. Using the mouse model, we identified 15 specific subtypes of cells in the liver tissue, including endothelial cells, hepatocytes, cholangiocytes, and hepatic stellate cells. Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations; led to marked inflammatory response, apoptosis and fatty acid metabolism dysfunction in hepatocytes; activated hepatic stellate cells; brought about the activation, inflammation, and phagocytosis of liver capsular macrophages cells; resulted in immune dysfunction of liver lymphocytes; disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways. Thus, these findings elaborate the mechanism underlying TGT-induced acute liver injury, provide new insights into the safe and rational applications in the clinic, and complement the identification of new biomarkers and therapeutic targets for liver protection. (c) 2023 The Authors. Published by Elsevier B.V. on behalf of Xi'an Jiaotong University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Tripterygium glycosides tablet Acute liver injury scRNA-seq

SCI

English

Corresponding

National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Establishment of Sino-Austria[2020YFE0205100] ; National Natural Science Foundation of China["82104480","82004248","82141001","82274182","82074098","82173914"] ; Fundamental Research Funds for the Central public welfare research institutes["ZZ14- YQ-055","ZZ14-YQ-059","ZZ14-YQ-060","ZXKT19018","ZXKT19021","ZXKT19022","ZZ14-YQ-050","ZZ14-YQ-051","ZZ14-YQ-052","ZZ14-FL002","ZZ14-ND-010","ZZ15-ND-10","ZZ16-ND-10-19"] ; Beijing Municipal Natural Science Foundation[7214287] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; Young Elite Scientists Sponsorship Program by CACM[2021QNRC2B29] ; CACMS Innovation Fund["CI2021A05101","CI2021A05104"] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences[CI2021B014] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties[SZGSP001] ; State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open~Fund[SKL2020Z0302]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001070502900001

ELSEVIER

Web of Science

1.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
2.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
3.Tianjin Univ Tradit Chinese Med, Sch Chinese Mat Med, Tianjin 301617, Peoples R China
4.Tianjin Univ Tradit Chinese Med, State Key Lab Component Based Chinese Med, Tianjin 301617, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Nephrol,Shenzhen Key Lab Kidney Dis,Shenzhen, Shenzhen 518020, Guangdong, Peoples R China
6.Bohai Univ, Inst Ocean, Coll Food Sci & Engn, Jinzhou 121013, Liaoning, Peoples R China
7.Chinese Ctr Dis Control & Prevent, Natl Inst Communicable Dis Control & Prevent, Collaborat Innovat Ctr Diag & Treatment Infect Dis, State Key Lab Infect Dis Prevent & Control, Beijing 102206, Peoples R China
8.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
9.Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen 518033, Guangdong, Peoples R China

Guo, Qiuyan,Wu, Jiangpeng,Wang, Qixin,et al. Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice[J]. JOURNAL OF PHARMACEUTICAL ANALYSIS,2023,13(8).

Guo, Qiuyan.,Wu, Jiangpeng.,Wang, Qixin.,Huang, Yuwen.,Chen, Lin.,...&Wang, Jigang.(2023).Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice.JOURNAL OF PHARMACEUTICAL ANALYSIS,13(8).

Guo, Qiuyan,et al."Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice".JOURNAL OF PHARMACEUTICAL ANALYSIS 13.8(2023).