Hepatic Cell News Volume 3.47 | Dec 13 2019

TOP STORY

Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis

ADAM metallopeptidase domain 17 (ADAM17)-mediated MerTK cleavage in liver macrophages decreased during steatosis to nonalcoholic steatohepatitis (NASH) transition, and mice with a cleavage-resistant MerTK mutant had increased NASH fibrosis. Macrophage MerTK promoted an ERK-TGFβ1 pathway that activates hepatic stellate cells and induced liver fibrosis. [Cell Metab] Abstract | Graphical Abstract

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Hypoxia Regulates the Mitochondrial Activity of Hepatocellular Carcinoma Cells through HIF/HEY1/PINK1 Pathway

From transcriptome sequencing, researchers found that HEY1, a transcriptional repressor, in the NOTCH pathway was consistently induced by hypoxia in hepatocellular carcinoma cell lines. They identified a strong hypoxia response element in HEY1 by chromatin immunoprecipitation and luciferase reporter assays. [Cell Death Dis] Full Article

Circ_0001955 Facilitates Hepatocellular Carcinoma (HCC) Tumorigenesis by Sponging miR-516a-5p to Release TRAF6 and MAPK11

A novel circRNA circ_0001955 was identified from three GSE datasets as a differentially expressed circRNA between HCC and normal samples. Investigators revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. [Cell Death Dis] Full Article

Dual TBK1/IKKɛ Inhibitor Amlexanox Attenuates the Severity of Hepatotoxin-Induced Liver Fibrosis and Biliary Fibrosis in Mice

Amlexanox treatment suppressed HSC activation and its related fibrogenic responses by partially inhibiting signal transducer and activator of transcription 3. Furthermore, amlexanox decreased the activation and inflammatory responses in Kupffer cells. [J Cell Mol Med] Full Article

Synergy of Phospholipid-Drug Formulations Significantly Deactivates Profibrogenic Human Hepatic Stellate Cells

The authors compared the ability of essential phosopholipids (EPLs) to restore quiescent-like features in HSCs with that of dilinoleoylphosphatidylcholine, polyenylphosphatidylcholine (PPC) fraction’s main component. Specifically, they screened at the cellular level the antifibrotic effects of PPC formulations in the presence and absence of silymarin, by using LX-2 cell and by assessing the main biochemical hallmarks of the activated and deactivated states of this cell line. [Pharmaceutics] Full Article | Graphical Abstract

Beclin 1 Deficiency Causes Hepatic Cell Apoptosis via Endoplasmic Reticulum Stress in Zebrafish Larvae

Scientists found accumulated protein aggregates and vigorous apoptosis in mutant larvae, predominantly in the liver. The hepatic cell apoptosis in mutants results from an endoplasmic reticulum stress response, however, it is not the leading cause of mutant larval lethality. [FEBS Lett] Abstract

Screening Hub Genes as Prognostic Biomarkers of Hepatocellular Carcinoma by Bioinformatics Analysis

The expression profiles of GSE121248, GSE45267 and GSE84402 were obtained from the Gene Expression Omnibus, including 132 hepatocellular carcinoma (HCC) and 90 noncancerous liver tissues. Differentially expressed genes between HCC and noncancerous samples were identified by GEO2 R and Venn diagrams. [Cell Transplant] Full Article

TGM3 Promotes Epithelial-Mesenchymal Transition and Hepatocellular Carcinogenesis and Predicts Poor Prognosis for Patients after Curative Resection

Investigators evaluated the role of TGM3 in regulating HCC cell proliferation, migration, and invasion. They also investigated the prognostic significance of TGM3 in an hepatocellular carcinoma (HCC) cohort. Finally, they explored the signaling pathways that TGM3 regulates in HCC. [Dig Liver Dis] Abstract

Circular RNA Expression Profiles following MC-LR Treatment in Human Normal Liver Cell Line (HL7702) Cells Using High-Throughput Sequencing Analysis

Researchers investigated whether circRNAs were involved in microcystin-LR (MC-LR)-mediated hepatotoxicity using human normal liver cell line. Using high-throughput sequencing analysis data demonstrated that expression levels of 3250, 3111, 3097, 3253 circRNAs were significantly altered at concentrations ranging from 1 to 10 µM MC-LR. Expression levels of hsa_circRNA_0000657 and hsa_circRNA_0000659 were down-regulated while hsa_circRNA_0003247 and hsa_circRNA_0001535 were up-regulated in all MC-LR-exposed groups. [J Toxicol Environ Health A] Abstract

Metformin-Induced Increases in GDF15 Are Important for Suppressing Appetite and Promoting Weight Loss

Scientists showed, using unbiased transcriptomics of mouse hepatocytes and analysis of proteins in human serum, that metformin induced expression and secretion of growth differentiating factor 15 (GDF15). In primary mouse hepatocytes, metformin stimulates the secretion of GDF15 by increasing the expression of activating transcription factor 4 and C/EBP homologous protein. [Nat Metab] Abstract

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A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

The authors underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: biological and synthetic scaffolds; animal and human tissue decellularization; scaffold recellularization; 3D bioprinting; and organoid technology. [Biomolecules] Abstract | Download Full Article

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Umecrine Cognition Announces Completion of Enrollment in Clinical Phase IIa Study with Golexanolone in Patients with Liver Cirrhosis and Hepatic Encephalopathy

Umecrine Cognition AB announced that enrollment has been completed in its Phase IIa study designed to assess the safety, pharmacokinetics and potential benefit of golexanolone, a novel GABAA receptor modulating steroid antagonists in development for treatment of hepatic encephalopathy in patients with liver cirrhosis. [Umecrine Cognition AB] Press Release

Congratulations to the 2020 SOT Award Recipients

The Society of Toxicology (SOT) announced the 2020 SOT award recipients. This year’s honorees come from a variety of backgrounds, educational experiences, and career paths and are recognized for their immense contributions to toxicology, including work related to better understanding the toxicological effects on liver injury and disease, immune system function, and reproductive and development health. [The Society of Toxicology] Press Release

NIH Strategic Plan Details Pathway to Achieving Hepatitis B Cure

A new strategic plan from the National Institutes of Health outlines efforts to intensify ongoing HBV research with the goals of developing a cure and improving scientific understanding of the virus while creating improved strategies for screening and treating patients. [National Institutes of Health News] Editorial

UK Election Dashes Scientists’ Hopes of Staying in the EU

The United Kingdom is now firmly on the path towards leaving the European Union, after the Conservative party won a majority of 79 seats in yesterday’s general election – a result that has major implications for science. [Nature News] Editorial

United States Drops Charges against Two More Scientists after Iran Prisoner Swap

US authorities have dropped charges against two researchers accused of attempting to export chemicals to Iran in violation of trade sanctions. The decision follows a prisoner swap in which the United States freed a third researcher who was charged alongside them – and imprisoned. [Nature News] Editorial

NEW Canadian Liver Meeting 2020
January 28-March 1, 2020
Montreal, Quebec, Canada

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NEW Lab Technician – Immunometabolism (Karolinska Institutet)

Postdoctoral Fellow – Liver Pathology (University of Illinois at Chicago)

Professor – Hepatology (Jena University Hospital)

Postdoctoral Researcher – HIV and the Liver (Seattle’s Children’s Hospital)

Postdoctoral Researcher – Oncogenic Pathways (University of Liège)

Faculty Member – Pathogen-Associated Malignancies (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Drug-Induced Liver Injury (Johnson & Johnson)

Postdoctoral Researcher – Personalized Medicine (Mayo Clinic Center for Individualized Medicine)

Postdoctoral Scientist – RAS Cancer Biology (Genetech, Inc.)

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