Supplmentary Materials, Methods, Figures and Tables
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Supplmentary Materials, Methods, Figures and Tables

SEEK ID: https://seek.lisym.org/data_files/521?version=1

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Seddik Hammad

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Seddik Hammad

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Created: 13th Dec 2021 at 09:46

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Version 1 (earliest) Created 13th Dec 2021 at 09:46 by Seddik Hammad

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Seddik Hammad

Projects: LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM network, LiSyM PALs, LiSyM-Krebs Partnering, C-TIP-HCC network, Forschungsnetzwerk LiSyM-Krebs

Institutions: Molecular Hepatology - Dept of Medicine II - Medical Faculty Mannheim - Heidelberg University

Expertise: Animal experimentalist, Imaging and image analysis, Omics

Tools: Animal facility, Microarray analysis, confocal microscopy, Metabolomics

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LiSyM: Liver Systems Medicine

Liver Systems Medicine : striving to develop non-invasive methods for diagnosing and treating NAFLD by combining mathematical modeling and biological research. LiSyM, is a multidisciplinary research network, in which molecular and cell biologists, clinical researchers, pharmacologists and experts in mathematical modeling examine the liver in its entirety. LiSyM research focuses on the metabolic liver disease non-alcoholic fatty liver disease (NAFLD), which includes non-alcoholic steatohepatitis ...

Projects: LiSyM Core Infrastructure and Management (LiSyM-PD), LiSyM Pillar I: Early Metabolic Injury (LiSyM-EMI), LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM Pillar III: Regeneration and Repair in Acute-on-Chronic Liver Failure (LiSyM-ACLF), LiSyM Pillar IV: Liver Function Diagnostics (LiSyM-LiFuDi), Model Guided Pharmacotherapy In Chronic Liver Disease (LiSyM-MGP), Molecular Steatosis - Imaging & Modeling (LiSyM-MSIM), The Hedgehog Signalling Pathway (LiSyM-JGMMS), Multi-Scale Models for Personalized Liver Function Tests (LiSyM-MM-PLF), LiSyM PALs, Project Management PTJ, LiSyM network, LiSyM Scientific Leadership Team (LiSyM-LT)

Web page: https://www.lisym.org/

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LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP)

In one in five people with NAFLD, the functioning liver cells, the hepatocytes, are replaced by connective tissue. Eventually this fibrosis becomes irreversible. In this state the liver is like a ‘scar that never heals’. Through it, the liver loses many of its vital functions. LiSyM-Pillar II wants to know more about which factors promote fibrosis and the conditions under which fibrosis becomes irreversible How can fibrosis be diagnosed as early as possible? Researchers in the pillar are also ...

Programme: LiSyM: Liver Systems Medicine

Public web page: http://www.lisym.org/our-work/pillar-research

Start date: 1st Jan 2016

Organisms: Mus musculus, Rattus rattus, Rattus norvegicus, Homo sapiens

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Julia/Yan

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP)

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Seddik Hammad

Pillar II dooley

Submitter: Seddik Hammad

Studies: CCl4 Treatment in mice

Assays: Metabolic CCl4

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Created: 21st Nov 2017 at 14:57

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CCl4 Treatment in mice

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP)

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Seddik Hammad

No description specified

Submitter: Seddik Hammad

Investigation: Julia/Yan

Assays: Metabolic CCl4

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Created: 21st Nov 2017 at 14:58, Last updated: 9th Feb 2018 at 12:26

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Metabolic CCl4

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP)

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Seddik Hammad

No description specified

Submitter: Seddik Hammad

Assay type: Proteomics

Technology type: FACS

Investigation: Julia/Yan

Study: CCl4 Treatment in mice

Organisms: Mus musculus

SOPs: Sample Collection and Preservation of Blood and...

Data files: Movies for quantification, SAC mice RNA microarray, Supp MM 1, Supp fig 3, Supp fig1, Supp fig2, Supplemental Table 1:, Supplemental Table 2, Supplmentary Materials, Methods, Figures and Ta... and 1 hidden item

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Created: 21st Nov 2017 at 15:02, Last updated: 13th Dec 2021 at 09:46

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

LiSyM Pillar II: Chronic Liver Disease Progression (LiSyM-DP), LiSyM network

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Seddik Hammad

Jieling Zhao

Steven Dooley

Abstract (Expand)

BACKGROUND & AIMS: Activation of transforming growth factor beta (TGFB) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanism of TGFB activation are not clear. We … investigated the role of extracellular matrix protein 1 (ECM1), which interacts with extracellular and structural proteins, in TGFB activation in livers of mice. METHODS: We performed studies with e C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1Deltahep). ECM1 or soluble TGFB receptor 2 (TGFBR2) were expressed in livers of mice following 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 liver were analyzed by immunohistochemistry and in situ hybridization. RESULTS: 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 alphav 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 ECM1Deltahep 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. CONCLUSIONS: 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.

Authors: W. Fan, T. Liu, W. Chen, S. Hammad, T. Longerich, Y. Fu, N. Li, Y. He, C. Liu, Y. Zhang, Q. Lian, X. Zhao, C. Yan, L. Li, C. Yi, Z. Ling, L. Ma, X. Zhao, H. Xu, P. Wang, M. Cong, H. You, Z. Liu, Y. Wang, J. Chen, D. Li, L. Hui, S. Dooley, J. Hou, J. Jia, B. Sun