Hepatic Cell News Volume 1.17 | May 26 2017

TOP STORY

Syndecan-1 Limits the Progression of Liver Injury and Promotes Liver Repair in Acetaminophen-Induced Liver Injury

Researchers examined the role of syndecan-1, the major cell surface heparan sulfate proteoglycan of hepatocytes, in acetaminophen (APAP)-induced liver injury. Their results demonstrated that 2-O-sulfated domains in syndecan-1 heparan sulfate halted disease progression and promoted liver repair by enhancing hepatocyte survival in APAP-induced liver injury. [Hepatology] Abstract

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Hepatocyte-Specific Sirtuin 6 Deletion Predisposes to Nonalcoholic Steatohepatitis by Up-Regulation of Bach1, an Nrf2 Repressor

To explore the role of hepatocyte sirtuin (Sirt) 6 in nonalcoholic steatohepatitis development, the authors generated hepatocyte-specific Sirt6 knockout mice that were fed a high-fat and high-fructose diet for 16 weeks. They discovered that Sirt6, which interacts with Bach1 under basal condition, induces its detachment from the antioxidant response element region of heme oxygenase 1 promoter. [FASEB J] Abstract

Activated Hepatic Stellate Cells Secrete Periostin to Induce Stem Cell-Like Phenotype of Residual Hepatocellular Carcinoma Cells after Heat Treatment

Scientists assessed whether activated hepatic stellate cells (HSCs) could regulate stem cell-like property of residual tumor after incomplete thermal ablation to promote tumor progression. Conditional medium from activated primary HSCs or LX-2 cells significantly induced the stem cell-like phenotypes of residual hepatocellular carcinoma cells after heat treatment. [Sci Rep] Full Article

The Let-7/Lin28 Axis Regulates Activation of Hepatic Stellate Cells in Alcoholic Liver Injury

Investigators evaluated the role of the let-7/lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells (HSCs) in alcoholic liver injury. They identified that ethanol feeding significantly downregulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Lin28b deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury [J Biol Chem] Abstract | Full Article

A Pump-Free Microfluidic 3D Perfusion Platform for the Efficient Differentiation of Human Hepatocyte-Like Cells

Researchers developed a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells. They performed on-chip differentiation of HepaRG, a human bipotent progenitor cell, and discovered that 3D microperfusion greatly enhances the hepatocyte differentiation efficiency over static 2D and 3D cultures. [Biotechnol Bioeng] Abstract

Long Non-Coding RNA MALAT1 Regulates ZEB1 Expression by Sponging miR-143-3p and Promotes Hepatocellular Carcinoma Progression

Scientists explored the effects of long non-coding RNA MALAT1 on hepatocellular carcinoma development. ZEB1 was a target of miR-143-3p. MiR-143-3p bound with MALAT1, and was regulated by MALAT1. The regulation of MALAT1 on ZEB1 was mediated by miR-143-3p. [J Cell Biochem] Abstract

High-Fat Diet Inhibits PGC-1α Suppressive Effect on NFκB Signaling in Hepatocytes

The authors investigated the role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) in the inflammatory changes observed in steatohepatitis induced by high-fat diet. The high-fat diet led to a state of nonalcoholic steatohepatitis, associated with increased deposits of intra-abdominal fat, hyperglycemia and hyperlipidemia. [Eur J Nutr] Abstract

MiR-145 Mediates Zebrafish Hepatic Outgrowth through Progranulin A Signaling

Researchers demonstrated a significant decrease in microRNA (miR)-145 expression during hepatogenesis. They modulated miR-145 expression in zebrafish embryos by injection with a miR-145 mimic or a miR-145 hairpin inhibitor. They confirmed a critical role of miR-145 in hepatic outgrowth by using whole-mount in situ hybridization. [PLoS One] Full Article

LncRNA-AF113014 Promotes the Expression of Egr2 by Interaction with miR-20a to Inhibit Proliferation of Hepatocellular Carcinoma Cells

Investigators identified AF113014 as a new long non-coding RNA (lncRNA) by Microarray. They found that AF113014 was differentially expressed between hepatocellular carcinoma (HCC) cell lines and normal hepatocytes. Functionally, AF113014 inhibited proliferation of HCC cells both in vitro and in vivo, whereas the opposite effect was observed when AF113014 knockdown. [PLoS One] Full Article

LAMC1 mRNA Promotes Malignancy of Hepatocellular Carcinoma Cells by Competing for MicroRNA-124 Binding with CD151

Scientists confirmed a miR-124 mediated competing endogenous RNA crosstalk between LAMC1 and CD151 in hepatocellular carcinoma (HCC). MiR-124 negatively regulated LAMC1 expression through two miRNA binding sites within its 3′ untranslated region and suppressed migration and invasion of HCC cells through regulating LAMC1. [IUBMB Life] Abstract

Roles of Diacylglycerols and Ceramides in Hepatic Insulin Resistance

The putative roles for diacylglycerols (DAGs) and ceramides in hepatic insulin resistance have proved more complex than originally imagined, with various genetic and pharmacologic manipulations yielding a vast and occasionally contradictory trove of data to sort. Researchers examine the state of this field, turning a critical eye toward both DAGs and ceramides as putative mediators of lipid-induced hepatic insulin resistance. [Trends Pharmacol Sci] Abstract

Understanding Liver Regeneration to Bring New Insights to the Mechanisms Driving Cholangiocarcinoma

The authors summarize the work which has led to the current understanding of the cellular source of cholangiocarcinoma, how the tumor recruits, sustains and is educated by its supporting stromal environment, and the tumor-derived signals that drive the progression and invasion of the cancer. [NPJ Regen Med] Full Article

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

U.S. Food and Drug Administration Accepts for Priority Review Bristol-Myers Squibb’s Application for Opdivo (Nivolumab) in Previously Treated Hepatocellular Carcinoma

Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) accepted a supplemental Biologics License Application that seeks to extend the use of Opdivo to patients with hepatocellular carcinoma (HCC) after prior sorafenib therapy. The FDA granted the application priority review and previously granted Opdivo orphan-drug designation for the treatment of HCC. [Bristol-Myers Squibb Company] Press Release

OICR Launches Five All-Star Teams of Ontario Scientists to Tackle Some of the Deadliest Forms of Cancer

Reza Moridi, Ontario’s Minister of Research, Innovation and Science announced that the Institute is funding five collaborative, cross-disciplinary and inter-institutional Translational Research Initiatives with a total of $24 million over the next two years. [Ontario Institute for Cancer Research (OICR)] Press Release

Fractyl Announces Initiation of Multicenter Clinical Trial to Evaluate a Novel Medical Procedure for Poorly Controlled Type 2 Diabetes

Fractyl Laboratories Inc. (Fractyl) announced that the first patient in Europe has been treated as part of a clinical trial called Revita-2. The trial is designed to evaluate the safety and efficacy of the Revita™ DMR System in orally-treated type 2 diabetes patients with poorly controlled disease. [Fractyl Laboratories Inc.] Press Release

FDA Approves First Cancer Treatment for Any Solid Tumor with a Specific Genetic Feature

The U.S. Food and Drug Administration granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker). This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated. [U.S. Food and Drug Administration] Press Release | Editorial

How NSF Cut 11% from Its Budget

Donald Trump planned to include an 11% cut to National Science Foundation’s (NSF’s) $7.4 billion budget in his first full spending request to Congress. The news—which was publicly unveiled as part of the president’s $4.1 trillion budget for 2018—sent Jim Olds, who leads the biology directorate at the NSF, and the heads of NSF’s other six research and education programs scrambling to erase big chunks of their portfolios without sacrificing NSF’s ability to fund the best new ideas. [ScienceInsider] Editorial

Fund to Curb Outbreaks and Chronic Disease on the Chopping Block

The Centers for Disease Control and Prevention stands to lose 12% of its budget through proposed cuts in the American Health Care Act. [Nature News] Editorial

Colombian Biologist Cleared of Criminal Charges for Posting Another Scientist’s Thesis Online

A Colombian biologist who faced a criminal trial for posting another scientist’s thesis online has been cleared of copyright violation — an offense that, under Colombian law, might have brought him a jail sentence. [Nature News] Editorial

Academies Calculate How Much Brexit Will Cost U.K. Researchers

Some academic fields in the United Kingdom (U.K.) will have major funding holes to fill once the country leaves the European Union, according to new research commissioned by four U.K. academies. [ScienceInsider] Editorial

Vaccine Could Soon Be Enlisted in the Fight against Ebola in the DRC

The Democratic Republic of the Congo has moved a step closer to using an unlicensed vaccine to battle an Ebola outbreak that began last month in a remote northeastern part of the country. The country’s government submitted a formal vaccine trial protocol, developed with Epicentre, the Paris-based research arm of Doctors Without Borders, to an ethical review board. [Science Insider] Editorial

NEW Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond
September 24-27, 2017
Orlando, United States

NEW Intestinal Organoid Virtual Training
October 17-25, 2017
None, None

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NEW Postdoctoral Studies – Liver Functions (Karolinska Instituet)

Postdoctoral Position – Novel Molecular and Cellular Mechanisms of Liver and Pancreatic Carcinogenesis (University of Illinois College of Medicine)

Assistant Professor – Renal and Hepatic Pharmacology (University of Manitoba)

Chief – Division of Gastroenterology and Hepatology (University of Nebraska Medical Center)

Postdoctoral Fellow – Obesity-Associated Complications (University of Kentucky College of Medicine)

Postdoctoral Position – Pediatrics/Cell Biology (Washington University School of Medicine)

Postdoctoral Fellow – Nonalcoholic Fatty Liver Disease Research (University of Groningen)

Scientist – Hepatic Nuclear Receptor Biology (Moderna Therapeutics)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease Research (University of Groningen)

Research Lead – Liver Discovery (Spark Therapeutics)

Research Technician II – Translational Liver Cancer (Fred Hutchinson Cancer Research Center)

Academic Surgical Pathologist – Liver/Gastrointestinal (Brigham and Women’s Hospital)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

Associate or Full Professor – Gastroenterology (University of Washington)

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