Hepatic Cell News Volume 2.11 | Mar 23 2018

TOP STORY

Hepatocyte-Secreted DPP4 in Obesity Promotes Adipose Inflammation and Insulin Resistance

Researchers showed that obesity in mice stimulates hepatocytes to synthesize and secrete dipeptidyl peptidase 4 (DPP4), which acts with plasma factor Xa to inflame adipose tissue macrophages. Silencing expression of DPP4 in hepatocytes suppressed inflammation of visceral adipose tissue and insulin resistance; however, a similar effect was not seen with the orally administered DPP4 inhibitor sitagliptin. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Aortic Carboxypeptidase-Like Protein, a WNT Ligand, Exacerbates Nonalcoholic Steatohepatitis

Scientists demonstrated that the hepatic expression of aortic carboxypeptidase–like protein (ACLP), a glycosylated, secreted protein, increases in nonalcoholic steatohepatitis (NASH) in humans and mice. Furthermore, they elucidated that ACLP is a ligand, unrelated to WNT proteins, that activates the canonical WNT pathway and exacerbates NASH pathology. [J Clin Invest] Full Article

HMGB1 Links Chronic Liver Injury to Progenitor Responses and Hepatocarcinogenesis

Investigators tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in chronic liver disease. While liver-specific HMGB1 deficiency did not significantly affect chronic injury responses such as fibrosis, regeneration and inflammation, it inhibited ductular/progenitor cell expansion and hepatocyte metaplasia. [J Clin Invest] Abstract | Full Article

Notch2 Controls Hepatocyte-Derived Cholangiocarcinoma Formation in Mice

Researchers generated NEMO^Δhepa/CcnE1^−/− and NEMO^Δhepa/CcnE2^−/− double knockout mice and investigated age-dependent liver disease progression in these animals. Deletion of CcnE1 in NEMO^Δhepa mice decreased basal liver damage and reduced spontaneous liver inflammation in young mice. [Oncogene] Abstract

Epigenetic Restriction of Hippo Signaling by MORC2 Underlies Stemness of Hepatocellular Carcinoma Cells

The authors report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma. They identified a member of the microrchidia (MORC) protein family, MORC2, as an inhibitor of the Hippo pathway by controlling upstream Hippo regulators, neurofibromatosis 2 and kidney and brain protein. [Cell Death Differ] Abstract

Functional Modulation of Gene Expression by Ultraconserved Long Non-Coding RNA TUC338 during Growth of Human Hepatocellular Carcinoma

TUC338 is an ultraconserved long non-coding RNA that contributes to transformed cell growth in hepatocellular carcinoma. TUC338 RNA-based purification was used to isolate chromatin for mass spectrometry, and the plasminogen activator inhibitor-1 RNA-binding protein was identified as a TUC338 RNA-binding partner. [iScience] Full Article | Graphical Abstract

PFKFB3 Blockade Inhibits Hepatocellular Carcinoma Growth by Impairing DNA Repair through AKT

Scientists found that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression is associated with hepatocellular carcinoma (HCC) growth and located mainly in the nucleus of tumor cells. Knockdown of PFKFB3 inhibited HCC growth, not only by reducing glucose consumption but also by damaging the DNA repair function, leading to G2/M phase arrest and apoptosis. [Cell Death Dis] Full Article

β2 Spectrin-Mediated Differentiation Repressed the Properties of Liver Cancer Stem Cells through β-Catenin

The authors investigated whether the disruption of βII-Spectrin (β2SP) contributed to tumorigenesis of hepatocellular carcinoma (HCC) through the dedifferentiation. Down-regulation of β2SP in hepatocytes was observed in cirrhotic liver and HCC. [Cell Death Dis] Full Article

The Nuclear Orphan Receptor Nur77 Alleviates Palmitate-Induced Fat Accumulation by Down-Regulating G0S2 in HepG2 Cells

Using human HepG2 hepatoma cells, researchers aimed to investigate the functional role of Nur77 in palmitate-induced hepatic steatosis. They revealed that palmitate significantly induced lipid accumulation and suppressed lipolysis in hepatocytes. [Sci Rep] Full Article

Delta-Like 3 Is Silenced by HBx via Histone Acetylation in HBV-Associated HCCs

Scientists showed that silencing of Delta-like 3 (DLL3) during hepatocarcinogenesis is closely related to viral infection, especially hepatitis B virus (HBV) infection. Treatment of cells with a histone deacetylase inhibitor induced DLL3 expression in HepG2.2.15 cells. [Sci Rep] Full Article

Rap1b Enhances the Invasion and Migration of Hepatocellular Carcinoma Cells by Up-Regulating Twist 1

Investigators reported that Rap1b was significantly up-regulated in hepatocellular carcinoma tissues compared with the non-tumoral liver tissues. Overexpression of Rap1b promoted tumor growth and migration in vitro and tumor formation in vivo. [Exp Cell Res] Abstract

The Hedgehog Pathway in Nonalcoholic Fatty Liver Disease

The authors describe the hedgehog (Hh) pathway, summarize the evidence for its role in nonalcoholic fatty liver disease evolution, and discuss the potential role for Hh pathway inhibitors as therapies to prevent nonalcoholic steatohepatitis, cirrhosis and liver cancer. [Crit Rev Biochem Mol Biol] Abstract

The Roles of Protein Tyrosine Phosphatases in Hepatocellular Carcinoma

Researchers review the current knowledge on the involvement of protein tyrosine phosphatase (PTP) in hepatocellular carcinoma (HCC) and further discuss the possibility of targeting PTP in HCC. [Cancers (Basel)] Full Article

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

Diabetes Medicine Reduces Liver Fat in Nonalcoholic Fatty Liver Disease

Researchers found that empagliflozin, a newer treatment for type 2 diabetes, reduces liver fat in patients with NAFLD and diabetes. Results of the randomized controlled study, called the E-LIFT Trial, will be presented. [Press release from the Endocrine Society discussing research to be presented at the Endocrine Society’s 100^th Annual Meeting, Chicago] Press Release

Intercept Announces Multiple New Ocaliva^® (Obeticholic Acid) Data Presentations

Intercept Pharmaceuticals, Inc. announced that multiple obeticholic acid abstracts, including a late-breaking poster, “Long-Term Obeticholic Acid Treatment Associated with Reversal or Stabilization of Fibrosis/Cirrhosis in Patients with Primary Biliary Cholangitis,” will be presented. [Press release from Intercept Pharmaceuticals, Inc. discussing research to be presented at the 53^rd Annual Meeting of the European Association for the Study of the Liver (EASL), Paris] Press Release

Dr. Meritxell Huch reviews organoid culture and applications for intestinal, hepatic, and pancreatic tissues. Watch Now

Regeneron and Alnylam Pharmaceuticals Announce Collaboration to Discover New Treatments for Nonalcoholic Steatohepatitis (NASH)

Regeneron Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc. announced a collaboration to identify RNAi therapeutics for the chronic liver disease NASH and potentially other related diseases. [Alnylam Pharmaceuticals, Inc.] Press Release

Anticancer Agent LENVIMA^® (Lenvatinib Mesylate) Approved for Additional Indication of Unresectable Hepatocellular Carcinoma (HCC) in Japan, First Approval Worldwide for LENVIMA for HCC

Eisai Co., Ltd. and Merck announced that the multiple receptor tyrosine kinase inhibitor LENVIMA^® has been approved in Japan for unresectable hepatocellular carcinoma (HCC). [Eisai Co., Ltd.] Press Release

Final 2018 Budget Deal Should Help the National Science Foundation in 2019, Too

The 4% increase for the National Science Foundation (NSF) in Alexandria, Virginia, in the 2018 omnibus spending bill hammered out by congressional leaders may be modest next to what its peer science agencies received. But it does offer NSF officials more breathing room to fund some major initiatives starting next year. [ScienceInsider] Editorial

Final 2018 Budget Bill Eases Biomedical Researchers’ Policy Worries

The 2018 omnibus spending bill released is cheering biomedical researchers. Not only because of the 8.8% raise it gives the National Institutes of Health—its largest in 15 years—but also because it blocks or drops several proposed policy changes that had concerned the community. [ScienceInsider] Editorial

Expectations Are High for UKRI, the United Kingdom’s New £6 Billion Research Behemoth

Combine U.S. agencies akin to the National Institutes of Health, National Science Foundation, and National Endowment for the Humanities. Toss in some energy and innovation research and fuel it all with the largest boost in R&D spending in recent history. Then put one person in charge. That’s what the United Kingdom has done in a major reorganization of research funding that unites all the research councils that support U.K. science. [ScienceInsider] Editorial

HIV Researcher Is New Head of US Public-Health Agency

HIV researcher Robert Redfield will lead the Centers for Disease Control and Prevention, Secretary of Health and Human Services, Alex Azar announced. [Nature News] Editorial

NEW Goodbye Flat Biology: In Vivo Inspired Cancer Biology and Therapy
September 9-12, 2018
Berlin, Germany

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NEW Assistant/Associate Professor – Virology (Saint Louis University School of Medicine)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Postdoctoral Research Fellow – Liver Cancer Pathogenesis and Immunobiology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Human Liver Function (Karolinska Institutet)

Postdoctoral Research Associate – Hepatitis B Virology (Imperial College London)

Postdoctoral Scientist – Viral Vectored Vaccines for Hepatitis Infections (University of Oxford)

Postdoctoral Research Associate – Liver Diseases (University of Illinois at Chicago)

Postdoctoral Scientist – Acute-on-Chronic Liver Failure (Foundation for Liver Research)

Postdoctoral Research Scientist – Cancer Research (Cancer Research UK Beatson Institute)

Global Clinical Lead – Oncology (AstraZeneca)

Postdoctoral Research Scientist – Hepatocellular Carcinoma (Cancer Research UK Beatson Institute)

Lectureship – Stem Cell Biology and Regenerative Medicine (University of Edinburgh)

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