Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition  

作　　者：QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang 

机构地区：[1]School of Life Sciences,Beijing University of Chinese Medicine,Beijing 100029,China [2]School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 100029,China [3]State Key Laboratory of Medical Molecular Biology,Department of Molecular Biology and Biochemistry,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China

出　　处：《Chinese Journal of Natural Medicines》2024年第1期31-46,共16页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.82004045);the National High-Level Talents Special Support Program,the Fundamental Research Funds for the Central Universities(No.2023-JYB-XJSJJ009);the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202006);the Young Talents Promotion Project of China Association of Traditional Chinese Medicine(No.2020-QNRC2-01).

摘　　要：Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional Chinese medicine(TCM)formula,is known for treating gynecological diseases and liver fibrosis.Our previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis.However,the mechanisms by which SWT influences H19 remain unclear.Thus,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver.Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver.Notably,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular injury.This modulation collectively led to reduced ECM deposition.Through extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory pathways.Meanwhile,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver fibrosis.However,these protective effects of SWT were diminished with the overexpression of H19 in vivo.In conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关 键 词：Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs CYTOSKELETON ECM deposition 

分 类 号：R965[医药卫生—药理学]