BIOMAT Database Logo BIOMAT Database Logo

ECM1 Prevents Activation of Transforming Growth Factor β, Hepatic Stellate Cells, and Fibrogenesis in Mice. 2019

Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China; CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Activation of TGFB (transforming growth factor β) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers. We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Δhep). ECM1 or soluble TGFBR2 (TGFB receptor 2) were expressed in livers of mice after injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl4) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy livers were analyzed by immunohistochemistry and in situ hybridization. ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with αv integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl4-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl4-induced liver fibrosis was accelerated in ECM1Δhep mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl4-induced fibrosis in mice. ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008104 Liver Cirrhosis, Alcoholic FIBROSIS of the hepatic parenchyma due to chronic excess ALCOHOL DRINKING. Alcoholic Cirrhosis,Hepatic Cirrhosis, Alcoholic,Alcoholic Hepatic Cirrhosis,Alcoholic Liver Cirrhosis
D008106 Liver Cirrhosis, Experimental Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS. Hepatic Cirrhosis, Experimental,Cirrhoses, Experimental Liver,Cirrhosis, Experimental Liver,Experimental Liver Cirrhoses,Experimental Liver Cirrhosis,Liver Cirrhoses, Experimental,Experimental Hepatic Cirrhosis
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D002251 Carbon Tetrachloride A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed) Tetrachloromethane,Tetrachloride, Carbon
D006519 Hepatitis, Alcoholic INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS. Alcoholic Hepatitis,Chronic Alcoholic Hepatitis,Hepatitis, Alcoholic, Chronic,Alcoholic Hepatitis, Chronic,Chronic Alcoholic Hepatitides
D006525 Hepatitis, Viral, Human INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D). Viral Hepatitis, Human,Human Viral Hepatitides,Human Viral Hepatitis,Viral Hepatitides, Human
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.
February 2018, The American journal of the medical sciences,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Aryl Hydrocarbon Receptor Signaling Prevents Activation of Hepatic Stellate Cells and Liver Fibrogenesis in Mice.
September 2019, Gastroenterology,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
LRP6-CRISPR prevents activation of hepatic stellate cells and liver fibrogenesis in rats.
January 2020, American journal of translational research,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Transforming growth factor-β (TGF-β)-mediated connective tissue growth factor (CTGF) expression in hepatic stellate cells requires Stat3 signaling activation.
October 2013, The Journal of biological chemistry,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
CTRP3 attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.
May 2017, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Diosgenin attenuates hepatic stellate cell activation through transforming growth factor-β/Smad signaling pathway.
January 2015, International journal of clinical and experimental medicine,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Transforming growth factor‑β1 reduces apoptosis via autophagy activation in hepatic stellate cells.
September 2014, Molecular medicine reports,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Bezafibrate prevents hepatic stellate cell activation and fibrogenesis in a murine steatohepatitis model, and suppresses fibrogenic response induced by transforming growth factor-beta1 in a cultured stellate cell line.
October 2008, Hepatology research : the official journal of the Japan Society of Hepatology,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
Dilinoleoylphosphatidylcholine prevents transforming growth factor-beta1-mediated collagen accumulation in cultured rat hepatic stellate cells.
April 2002, The Journal of laboratory and clinical medicine,
Weiguo Fan, and Tianhui Liu, and Wen Chen, and Seddik Hammad, and Thomas Longerich, and Ingrid Hausser, and Yadong Fu, and Nan Li, and Yajing He, and Cui Liu, and Yaguang Zhang, and Qiaoshi Lian, and Xinhao Zhao, and Chenghua Yan, and Li Li, and Chunyan Yi, and Zhiyang Ling, and Liyan Ma, and Xinyan Zhao, and Hufeng Xu, and Ping Wang, and Min Cong, and Hong You, and Zhihong Liu, and Yan Wang, and Jianfeng Chen, and Dangsheng Li, and Lijian Hui, and Steven Dooley, and Jinlin Hou, and Jidong Jia, and Bing Sun
EphB2 receptor tyrosine kinase promotes hepatic fibrogenesis in mice via activation of hepatic stellate cells.
February 2018, Scientific reports,
Copied contents to your clipboard!