Single-cell transcriptomic dissection of the cellular and molecular events underlying the triclosan-induced liver fibrosis in mice  

作　　者：Yun-Meng Bai Fan Yang Piao Luo Lu-Lin Xie Jun-Hui Chen Yu-Dong Guan Hong-Chao Zhou Teng-Fei Xu Hui-Wen Hao Bing Chen Jia-Hui Zhao Cai-Ling Liang Ling-Yun Dai Qing-Shan Geng Ji-Gang Wang 

机构地区：[1]Department of Nephrology,Shenzhen Key Laboratory of Kidney Diseases,and Shenzhen Clinical Research Centre for Geriatrics,Shenzhen People’s Hospital,the First Affiliated Hospital,Southern University of Science and Technology,Shenzhen 518020,China [2]Department of Urology,Shenzhen People’s Hospital,the First Affiliated Hospital,Southern University Science and Technology,the Second Clinical Medical College,Jinan University,Shenzhen 518020,China [3]Integrated Chinese and Western Medicine Postdoctoral Research Station,Jinan University,Guangzhou 510632,China [4]Artemisinin Research Center,and Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China [5]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China [6]Center for Reproductive Medicine,Dongguan Maternal and Child Health Care Hospital,Southern Medical University,Dongguan 523125,Guangdong,China

出　　处：《Military Medical Research》2023年第5期599-619,共21页军事医学研究（英文版）

基　　金：supported by the National Key Research and Development Program of China(2020YFA0908000 and 2022YFC2303600);the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002);the National Natural Science Foundation of China(82141001,82274182,82173914,82074098,81903588 and 82003814);the Science and Technology Foundation of Shenzhen(JCYJ20210324115800001);the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases);the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZXKT18003);the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050);the National Key R&D Program of China Key projects for international cooperation on science,technology and innovation(2020YFE0205100);the Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034);the Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034);the Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234);the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(SZGSP001);the Shenzhen Key Laboratory of Kidney Diseases(ZDSYS201504301616234);the Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(SZGSP001);partially supported by a Grant from the Sanming Project of Medicine in Shenzhen(SZSM201612034).

摘　　要：Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing(scRNA-seq) was then carried out on TCS-or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor(TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis,the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells(HSCs)were significantly increased in TCS-treated group. We found that TCS promoted fibr

关 键 词：TRICLOSAN Single cell RNA sequencing Liver fibrogenesis Hepatic stellate cell 

分 类 号：R57[医药卫生—消化系统]