Hepatic Cell News Volume 4.14 | Apr 24 2020

TOP STORY

Parental Metabolic Syndrome Epigenetically Reprograms Offspring Hepatic Lipid Metabolism in Mice

Researchers used the liver-specific insulin receptor knockout mouse, a unique nondietary model manifesting three hallmarks that conferred high risk for the development of nonalcoholic fatty liver disease: hyperglycemia, insulin resistance, and dyslipidemia. They reported that parental metabolic syndrome epigenetically reprogrammed members of the TGF-β family, including neuronal regeneration-related protein and growth differentiation factor 15. [J Clin Invest] Full Article | Graphical Abstract

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HSPA12A Attenuates Lipopolysaccharide-Induced Liver Injury through Inhibiting Caspase-11-Mediated Hepatocyte Pyroptosis via Pgc-1α-Dependent Acyloxyacyl Hydrolase Expression

Scientists reported that cytosolic lipopolysaccharide (LPS) increased heat shock protein 12A (HSPA12A) nuclear translocation in hepatocytes, while knockout of HSPA12A (Hspa12a⁻/⁻) in mice promoted LPS-induced acute liver injury. [Cell Death Differ] Full Article

Hepatic Expression of Lipopolysaccharide Binding Protein (Lbp) Is Induced by the Gut Microbiota through Myd88 and Impairs Glucose Tolerance in Mice Independent of Obesity

Investigators demonstrated that the gut microbiota regulated hepatic expression of Lbp through myeloid differentiation primary response 88 (MYD88)-dependent signaling. LBP potentiated lipopolysaccharide inhibition of insulin signaling in vitro as well as impaired systemic glucose homeostasis in vivo. [Mol Metab] Full Article

Blocking GSDMD Processing in Innate Immune Cells but Not in Hepatocytes Protects Hepatic Ischemia-Reperfusion Injury

The authors demonstrated that pyroptosis in innate immune cells aggravated hepatic ischemia-reperfusion injury (IRI) and implied that hepatic IRI could be protected by blocking pyroptosis. Adopting caspase-1 inhibitors, they showed that inhibition of pyroptosis significantly ameliorated liver injury and suppressed inflammatory response during hepatic IRI. [Cell Death Dis] Full Article

MSCs Ameliorate Hepatocellular Apoptosis Mediated by PINK1-Dependent Mitophagy in Liver Ischemia/Reperfusion Injury through AMPKα Activation

Researchers found a novel pharmacological mechanism that mesenchymal stem cells (MSCs) exerted hepatoprotective effect in liver ischemia/reperfusion injury via upregulating PINK1-dependent mitophagy. This effect might be attributed to the modulation of AMPKα activation which was observed. [Cell Death Dis] Full Article

Protein Diaphanous Homolog 1 (Diaph1) Promotes Myofibroblastic Activation of Hepatic Stellate Cells by Regulating Rab5a Activity and TGFβ Receptor Endocytosis

Using shRNA to knockdown Diaph1 or SMIFH2 to target Diaph1 activity of hepatic stellate cells (HSCs), scientists found that Diaph1 inactivation blocked internalization and intracellular trafficking of transforming growth factor-beta (TGFβ1) receptor II and reduced SMAD3 phosphorylation induced by TGFβ1. [FASEB J] Full Article

Integration of miRNA-Regulatory Networks in Hepatic Stellate Cells Identifies TIMP3 as a Key Factor in Chronic Liver Disease

Several miRNAs targeting TIMP3 were upregulated in activated hepatic stellate cells (HSCs) and down-regulation of TIMP3 expression was associated with inflammatory activity in liver fibrosis and poor prognosis in hepatocellular carcinoma. [Liver Int] Abstract

Dimethyl Fumarate Ameliorates Hepatic Inflammation in Alcohol Related Liver Disease

Dimethyl fumarate (DMF) counteracted ethanol-induced intestinal barrier dysfunction, suppressed inflammatory responses of kupffer cells and ameliorated hepatic inflammation and steatosis, hallmarks of experimental alcohol-related liver disease (ALD). [Liver Int] Abstract

Construction of Higher-Order Cellular Microstructures by a Self-Wrapping Co-Culture Strategy Using a Redox-Responsive Hydrogel

Using human hepatocellular carcinoma spheroids as proof-of-concept, the authors suggested a strategy for constructing three-dimensional cellular architectures comprising viable cells. The strategy used a redox-responsive hydrogel and a confluent monolayer of cells cultured on the hydrogel surface, which peeled off and self-folded to wrap other cells. [Sci Rep] Full Article

Identifying Strategies to Target the Metabolic Flexibility of Tumors

Investigators identified the compensatory mechanisms following the inhibition of major pathways of central carbon metabolism in c-MYC-induced liver tumors. They found that, while inhibition of both glutaminase isoforms in tumors considerably delayed tumorigenesis, glutamine catabolism continued, owing to the action of amidotransferases. [Nat Metab] Abstract

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Lytic Cell Death in Metabolic Liver Disease

The authors summarize the underlying mechanism of distinct lytic cell death modes and their commonalities and discuss its relevance to metabolic liver diseases of different aetiologies, acknowledging the limitation of current knowledge in the field. [J Hepatol] Full Article

Pro-Inflammatory Signaling and Gut-Liver Axis in Non-Alcoholic and Alcoholic Steatohepatitis: Differences and Similarities Along the Path

Scientists examine the features and the pro-inflammatory pathways leading to non-alcoholic and alcoholic steatohepatitis. The involvement of several events and multiple inter-related pathways in the pathogenesis of these diseases suggest that a single therapeutic agent was unlikely to be an effective treatment strategy. [J Cell Mol Med] Full Article

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Celsion Reports that Sufficient Events Have Been Reached for the Second Interim Analysis of the Phase III OPTIMA Study of ThermoDox^® in Primary Liver Cancer

Celsion Corporation have announced that the prescribed minimum number of events of 158 patient deaths has been reached for the second pre-specified interim analysis of the OPTIMA Phase III Study with ThermoDox^® plus radiofrequency ablation in patients with hepatocellular carcinoma, or primary liver cancer. [Celsion Corporation] Press Release

VIR-2218 Demonstrates Dose-Dependent and Durable Reductions of Hepatitis B Surface Antigen in Phase I/II Trial

Vir Biotechnology, Inc. have announced additional interim data from the ongoing Phase II trial in patients and results from the Phase I trial in healthy volunteers of VIR-2218, an investigational small interfering ribonucleic acid that mediates RNA interference for the treatment of chronic hepatitis B virus infection. [Vir Biotechnology, Inc.] Press Release

Untapped Potential: More US Labs Could Be Providing Tests for Coronavirus

A survey of more than 4,000 researchers in the United States suggested that better coordination at an institutional and national level could make hundreds of thousands more coronavirus tests available. [Nature News] Editorial

Director of US Agency Key to Vaccine Development Leaves Role Suddenly Amid Coronavirus Pandemic

Rick Bright, one of the nation’s leading vaccine development experts and the director of the Biomedical Advanced Research and Development Authority, is no longer leading the organization. [STAT News] Editorial

Open Science Takes On the Coronavirus Pandemic

When reports emerged in late 2019 of an outbreak of a new coronavirus centred in Wuhan, China, researchers at the virological-analysis website Nextstrain were ready. The open-source project tracked the spread of viruses through genetic variations in the sequences that scientists find. [Nature News] Editorial

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NEW Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

NEW Postdoctoral Fellow – Molecular Diagnostics and Experimental Therapeutics (City of Hope)

NEW Professorship of Hepatology (Ludwig-Maximilians-Universität (LMU))

Senior Research Scientist – Liver Disease (Novo Nordisk)

Scientist – Molecular & Cellular Biology (Deep Genomics, Inc.)

Postdoctoral Position – Gut-Liver Axis (University of California, Davis)

Postdoctoral Position – Liver Pathogenesis (Washington University in St.Louis)

Therapuetic Specialist – Inflammation (Gilead Sciences Inc.)

Senior Postdoctoral Research Assistant – Liver Research (University of Dundee)

Team Leader – Cholangiocytes (Miromatrix Medical)

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