Hepatic Cell News Volume 1.00 | Jan 20 2017

TOP STORY

Circadian- and UPR-Dependent Control of CPEB4 Mediates a Translational Response to Counteract Hepatic Steatosis under ER Stress

Researchers showed that cytoplasmic polyadenylation element-binding (CPEB) 4 is required for adaptation to high-fat-diet- and ageing-induced endoplasmic reticulum (ER) stress, and subsequent hepatosteatosis. Combined transcriptional and translational Cpeb4 regulation generated a ‘circadian mediator’, which coordinated hepatic unfolded protein response activity with periods of high ER-protein-folding demand. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex

The authors showed that metformin robustly inhibits mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) in mouse liver tissue and primary hepatocytes. Using mouse genetics, they found that at the lowest concentrations of metformin that inhibit hepatic mTORC1 signaling, this inhibition is dependent on AMP-activated protein kinase (AMPK) and the tuberous sclerosis complex (TSC) protein complex (TSC complex). [Cell Metab] Abstract | Graphical Abstract

Farnesoid X Receptor Ablation Sensitizes Mice to Hepatitis B Virus X Protein–Induced Hepatocarcinogenesis

Scientists showed that hepatitis B virus X protein (HBx) can interact with farnesoid X receptor (FXR) and function as a coactivator of FXR. In vivo, FXR ablation markedly sensitized mice to HBx-induced hepatocarcinogenesis. [Hepatology] Abstract

An Endoplasmic Reticulum Protein, Nogo-B, Facilitates Alcoholic Liver Disease through Regulation of Kupffer Cell Polarization

Since endoplasmic reticulum (ER) stress is known to induce M2 macrophage polarization, the authors examined whether Nogo-B regulates M1/M2 polarization of Kupffer cells and alters the pathogenesis of alcoholic liver disease. Nogo-B in Kupffer cells promoted M1 polarization, whereas absence of Nogo-B increased ER stress and M2 polarization in Kupffer cells. [Hepatology] Abstract

The Microbiota Maintain Homeostasis of Liver-Resident γδT-17 Cells in a Lipid Antigen/CD1d-Dependent Manner

Investigators showed that hepatic IL-17A-producing γδ T (γδT-17) cells are liver-resident cells and predominant producers of IL-17A. The microbiota sustained hepatic γδT-17 cell homeostasis, including activation, survival and proliferation. Liver-resident γδT-17 cell homeostasis depended on hepatocyte-expressed CD1d, that presented lipid antigen, but not Toll-like receptors or IL-1/IL-23 receptor signaling. [Nat Commun] Full Article

The microRNA-449 Family Inhibits TGF-β-Mediated Liver Cancer Cell Migration by Targeting SOX4

Researchers demonstrated that the microRNA-449 family acts as tumor suppressor in liver cancer by causing cell death and inhibiting cell migration. These effects were caused by downregulation of the oncogene SOX4, which is frequently overexpressed in liver cancer. [J Hepatol] Abstract

RIPK1 Protects Hepatocytes from Kupffer Cells-Mediated TNF-Induced Apoptosis in Mouse Models of PAMP-Induced Hepatitis

Scientists investigated the role of the receptor interacting protein kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of pathogen associated molecular patterns (PAMP)-induced hepatitis. Whereas RIPK1 deficiency in liver parenchymal cells did not trigger basal hepatolysis, it greatly sensitized hepatocyte to apoptosis and to liver damages following single injection of lipopolysaccharide or CpG oligodeoxynucleotide. [J Hepatol] Abstract | Graphical Abstract

Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signaling

The authors identified a global and sex-dependent transcriptional de-regulation due to the block in cholesterol synthesis during development of the Cyp51 knockout mice and provided in vivo evidence that sterol intermediates downstream of lanosterol regulate the hepatic RORC activity. [Sci Rep] Full Article

Activation of Wnt/β-Catenin Signaling via GSK3 Inhibitors Direct Differentiation of Human Adipose Stem Cells into Functional Hepatocytes

Investigators suggested that activation of Wnt/β-catenin signalling via glycogen synthase kinase 3 (GSK3) inhibitors in definitive endoderm specification may represent an important mechanism mediating human adipose stem cells differentiated to functional hepatocyte. [Sci Rep] Full Article

MicroRNA-145 Promotes Activation of Hepatic Stellate Cells via Targeting Krüppel-Like Factor 4

Researchers aimed to characterize miR-145 and Krüppel-like factor 4 (KLF4) in activated hepatic stellate cells (HSCs) and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-β treated HSCs. [Sci Rep] Full Article

Biology and Function of Glypican-3 as a Candidate for Early Cancerous Transformation of Hepatocytes in Hepatocellular Carcinoma

The authors summarize current knowledge regarding the clinical aspects of glypican-3, while also synthesizing the current literature with the aim to better understand this molecule’s biological interactions at a molecular level, not only in the liver, but in the rest of the body as well. [Oncol Rep] Abstract

Visit our reviews page to see a complete list of reviews in the hepatic cell research field.

NeuroVive Presents Positive Preclinical Data in Hepatocellular Cancer at HCC Summit

NeuroVive Pharmaceutical AB announced that an abstract with novel preclinical cancer data related to the company’s sanglifehrin-based compounds has been accepted for presentation at a scientific conference. [Press release from NeuroVive Pharmaceutical AB discussing research to be presented at the 2017 European Association for the Study of the Liver (EASL) Hepatocellular Carcinoma (HCC) Summit, Geneva] Press Release

Can-Fite Receives IRB Approval to Commence Patient Enrollment in Phase II NAFLD/NASH Trial in Q1 2017

Can-Fite BioPharma Ltd. announced it has received approval to commence patient enrollment in a Phase II study of its liver drug candidate Namodenoson in the treatment of non-alcoholic fatty liver disease, the precursor to non-alcoholic steatohepatitis. [Can-Fite BioPharma Ltd.] Press Release

European Commission Grants Marketing Authorization for Gilead’s Vemlidy^® (Tenofovir Alafenamide, TAF) for the Treatment of Chronic Hepatitis B Virus Infection

Gilead Sciences, Inc. announced that the European Commission has granted marketing authorization for Vemlidy^®, a once-daily tablet for the treatment of chronic hepatitis B virus infection in adults and adolescents. [Gilead Sciences, Inc.] Press Release

Billion-Dollar Project Aims to Prep Vaccines before Epidemics Hit

SARS, Zika, Ebola – when some of the world’s most terrifying disease outbreaks occur, health workers often find themselves powerless. A billion-dollar initiative aims to change that situation by pre-emptively developing and stockpiling vaccines to combat potential epidemic threats. [Nature News] Editorial

Mystery as Controversial List of Predatory Publishers Disappears

A popular blog that lists “potential, possible, or probable predatory” publishers and journals has disappeared, but it is not clear why. A University of Colorado in Denver spokesperson told ScienceInsider that Beall made a “personal decision” to take down his list of low-quality journals that charge authors a fee to publish, often with little or no review or editing. [ScienceInsider] Editorial

NEW The European Association for the Study of the Liver (EASL) Hepatocellular Carcinoma (HCC) Summit
February 2-5, 2017
Geneva, Switzerland

NEW Keystone Symposium: Lipidomics and Bioactive Lipids in Metabolism and Disease
February 26-March 2, 2017
Tahoe City, United States

Visit our events page to see a complete list of events in the community.

NEW PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

NEW PhD Position – Pathogens Infecting Liver (Helmholtz Association)

NEW PhD Studentships – Liver Organ Growing (Downstate Medical Center)

NEW Postdoc/Research Associate – Liver Cancer (Icahn School of Medicine at Mount Sinai)

NEW Research Scientist – Liver Diseases (Gilead Sciences)

NEW Postdoctoral Research Fellow – Liver Genetics (National Jewish Health)

NEW Postdoctoral Research Fellow – Liver Cancer (Fred Hutchinson Cancer Research Center)

NEW Senior Scientist – Oncology (Genentech Research)

NEW Training Fellowship – Clinical Research (University of Oxford)

NEW Postdoctoral Associate – Cancer Biology (University of Florida)

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