Hepatic Cell News Volume 5.10 | Mar 19 2021

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    2021-03-19 | HCN 5.10


    Hepatic Cell News by STEMCELL Technologies
    Vol. 5.10 – 19 March, 2021
    TOP STORY

    TIPE1 Inhibits Hepatic Steatosis, Inflammation, and Fibrosis by Suppressing Polyubiquitination of ASK1

    Researchers showed that tumor necrosis factor alpha (TNF‐α)-induced protein 8‐like 1 (TIPE1) protects against hepatic steatosis, inflammation, and fibrosis through directly binding apoptosis signal‐regulating kinase 1 (ASK1) and restraining its TNF receptor-associated factor 6‐catalyzed polyubiquitination during the development of nonalcoholic steatohepatitis.
    [Hepatology]

    Abstract

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    PUBLICATIONSRanked by the impact factor of the journal

    Steatotic Hepatocytes Release Mature VLDL via Methionine and Tyrosine Metabolism in a Keap1‐Nrf2 Dependent Manner

    An imbalance between free fatty acids and Met and Tyr induced hepatic steatosis by disturbing the VLDL assembling via the Keap1‐Nrf2 system.
    [Hepatology]

    Abstract

    MED1 Mediator Subunit Is a Key Regulator of Hepatic Autophagy and Lipid Metabolism

    Investigators found that mediator complex subunit 1 (MED1) knockdown in cultured hepatic cells decreased autophagy and mitochondrial activity that was accompanied by decreased transcription of genes involved in these processes. Lipophagy and fatty acid β-oxidation also were impaired.
    [Autophagy]

    Abstract

    IRF2 Regulates Cellular Survival and Lenvatinib-Sensitivity of Hepatocellular Carcinoma (HCC) through Regulating β-Catenin

    Silencing Interferon regulatory factorsI (IRF2) downregulated the expression of β-catenin, while overexpressing IRF2 upregulated β-catenin. The expression of β-catenin and IRF2 was positively correlated in HCC tissues. Inhibiting β-catenin with XAV-939 effectively abrogated β-catenin expression caused by lenvatinib treatment.
    [Autophagy]

    Full Article

    Hepatic Stellate Cells Promote Intrahepatic Cholangiocarcinoma Progression via NR4A2/Osteopontin/Wnt Signaling Axis

    By establishing co-culture models of Intrahepatic cholangiocarcinoma (ICC) cells and hepatic stellate cells (HSCs), researchers identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells.
    [Oncogene]

    Abstract

    Matrix Metalloproteinase-1 Decorated Polymersomes, a Surface-Active Extracellular Matrix Therapeutic, Potentiates Collagen Degradation and Attenuates Early Liver Fibrosis

    The therapeutic effects of matrix metalloproteinase-1 (MMP-1) decorated polymersomes (MMPsomes), compared to MMP-1, were evaluated in vivo in carbon-tetrachloride-induced early liver fibrosis mouse model. MMPsomes exhibited favorable physicochemical properties, MMP-1 surface localization and improved therapeutic efficacy in TGFβ-activated human hepatic stellate cells in vitro.
    [Journal of Controlled Release]

    Full ArticleGraphical Abstract

    Dysregulation of MiR-23b-5p Promotes Cell Proliferation via Targeting FOXM1 in Hepatocellular Carcinoma

    Gain- or loss-of-function assays demonstrated that miR-23b-5p induced G0/G1 cell cycle arrest and inhibited cell proliferation both in vitro and in vivo. qRT-PCR, western blot and luciferase assays verified that Mammalian transcription factor Forkhead Box M1 (FOXM1), upregulated in hepatocellular carcinoma specimens, was negatively correlated with miR-23b-5p expression and acted as a direct downstream target of miR-23b-5p.
    [Cell Death Discovery]

    Full Article

    Gli2-Regulated Activation of Hepatic Stellate Cells and Liver Fibrosis by TGF-β Signaling

    Scientists investigated the effect of Gli2 on liver fibrogenesis and its possible mechanism using conditional knockout Gli2 mice and hepatic stellate cell models.
    [American Journal of Physiology-Gastrointestinal and Liver Physiology]

    Abstract

    5-Methoxytryptophan Alleviates Liver Fibrosis by Modulating FOXO3a/MiR-21/ATG5 Signaling Pathway Mediated Autophagy

    In vitro, 5-methoxytryptophan (5-MTP) treatment could inhibit TGF-β1-induced elevated levels of collagen I, collagen III, fibronectin and α-smooth muscle actin by stimulating autophagy process. Mechanically, the expression of FOXO3a was enhanced by 5-MTP and then repressed the level of miR-21, eventually leading to a restoration of autophagy-related gene ATG5.
    [Cell Cycle]

    Abstract


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    REVIEWS

    Role of the mTOR-Autophagy-ER Stress Pathway in High Fructose-Induced Metabolic-Associated Fatty Liver Disease

    This review discusses the possible molecular mechanisms of mammalian target of rapamycin (mTOR)-autophagy-endoplasmic reticulum (ER) stress in metabolic-associated fatty liver disease.
    [Acta Pharmacologica Sinica]

    Abstract

    The Role of N6-Methyladenosine Modification in the Life Cycle and Disease Pathogenesis of Hepatitis B and C Viruses

    The authors review the role of N6-methyladenosine (m6A) modification in hepatitis B virus (HBV)/hepatitis C virus (HCV) replication and its contribution to liver disease pathogenesis. A better understanding of the functions of m6A methylation in the life cycles of HBV and HCV is required to establish the role of these modifications in liver diseases associated with these viral infections.
    [Experimental and Molecular Medicine]

    Full Article

    INDUSTRY AND POLICY NEWS

    Genevant Sciences Announces Global Collaboration and License Agreement with Takeda to Develop Novel Nucleic Acid Therapeutics for Liver Fibrosis

    Genevant Sciences, announced that it has entered into a global collaboration and license agreement with Takeda Pharmaceutical Company Limited for the discovery, development and commercialization of LNP-delivered nucleic acid therapeutics directed to previously inaccessible drug targets in hepatic stellate cells to treat liver fibrosis.
    [Genevant Sciences]

    Press Release

    Versantis Announces Positive Phase Ib Results for VS-01 in Patients with Decompensated Cirrhosis

    Versantis announced positive results from a Phase Ib clinical trial of VS-01 in decompensated liver cirrhosis. VS-01 was found to be safe and well tolerated in this first-in-human, single ascending and multiple dose study led by Dr. Jonel Trebicka at the Goethe University Hospital Frankfurt.
    [Versantis]

    Press Release

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