Single-cell transcriptome analysis uncovers underlying mechanisms of acute liver injury induced by tripterygium glycosides tablet in mice
作者机构：State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di HerbsArtemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China School of Chinese Materia Medicaand State Key Laboratory of Component-Based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin301617China Department of NephrologyShenzhen Key Laboratory of Kidney DiseasesShenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalThe First Affiliated HospitalSouthern University of Science and TechnologyShenzhenGuangdong518020China College of Food Science and EngineeringInstitute of OceanBohai UniversityJinzhouLiaoning121013China State Key Laboratory of Infectious Disease Prevention and ControlCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Institute for Communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing100700China The Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhenGuangdong518033China
出 版 物：《药物分析学报:英文版》 (Journal of Pharmaceutical Analysis)
年 卷 期：2023年第13卷第8期
页 面：908-925页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：supported by the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600) the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(Grant No.:2020YFE0205100) the National Natural Science Foundation of China(Grant Nos.:82104480,82004248,82141001,82274182,82074098,82173914) the Fundamental Research Funds for the Central public welfare research institutes(Grant Nos.:ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,ZXKT19018,ZXKT19021,ZXKT19022,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10,ZZ16-ND-10-19) the Beijing Municipal Natural Science Foundation(Grant No.:7214287) the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002) the Young Elite Scientists Sponsorship Program by CACM(Grant No.:2021QNRC2B29) the CACMS Innovation Fund(Grant Nos.:CI2021A05101,CI2021A05104) the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014) the Science and Technology Foundation of Shenzhen(Grant No.:JCYJ20210324115800001) the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases) Shenzhen Governmental Sustainable Development Fund(Grant No.:KCXFZ20201221173612034) Shenzhen key Laboratory of Kidney Diseases(Grant No.:ZDSYS201504301616234) Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Grant No.:SZGSP001) the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002) the State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open Fund(Grant No.:SKL2020Z0302)
主 题：Tripterygium glycosides tablet Acute liver injury scRNA-seq
摘 要：Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii *** been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet s syndrome,leprosy reaction and autoimmune ***,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 *** present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)*** 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 *** the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate *** 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 ***,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.
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