Hepatic Cell News Volume 1.41 | Nov 10 2017

TOP STORY

How Chronic Inflammation Tips the Balance of Immune Cells to Promote Liver Cancer

Researchers found that chronic liver inflammation promotes cancer by suppressing immunosurveillance — a natural defense mechanism in which it’s thought the immune system suppresses cancer development. [Press release from the University of California, San Diego discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Hepatic Neuregulin 4 Signaling Defines an Endocrine Checkpoint for Steatosis-to-NASH Progression

Scientists showed that neuregulin 4 (Nrg4) is a key component of an endocrine checkpoint that preserves hepatocyte health and counters diet-induced NASH in mice. Nrg4 deficiency accelerated liver injury, fibrosis, inflammation, and cell death in a mouse model of nonalcoholic steatohepatitis (NASH). [J Clin Invest] Full Article | Press Release

Arid1a Regulates Response to Anti-Angiogenic Therapy in Advanced Hepatocellular Carcinoma

Researchers demonstrated that Arid1a deficiency, occurring in advanced human hepatocellular carcinomas (HCC), is associated with increased vessel density. Mechanistically, loss of Arid1a caused aberrant histone H3K27ac deposition at the angiopoietin-2 (Ang2) enhancer and promoter, which eventually leads to ectopic expression of Ang2 and promotes HCC development. [J Hepatol] Abstract | Graphical Abstract

WWC Proteins Regulate Hepatic Cell Differentiation and Tumorigenesis via the Hippo Signaling Pathway

Investigators showed that loss of hepatic WWC expression in mice leads to tissue overgrowth, inflammation, fibrosis and formation of liver carcinoma. WWC-deficient mouse livers display reduced LATS activity, increased YAP-mediated gene transcription and enhanced proliferation of hepatic progenitor cells. [Hepatology] Abstract

Interrogation of the Atherosclerosis-Associated SORT1 (Sortilin 1) Locus with Primary Human Hepatocytes, Induced Pluripotent Stem Cell-Hepatocytes, and Locus-Humanized Mice

Scientists compared three different hepatocyte models in demonstrating that the rs12740374 minor allele sequence is responsible for transcriptional activation of SORT1 expression. [Arterioscler Thromb Vasc Biol] Abstract

Effect of Human Amniotic Epithelial Cells on Pro-Fibrogenic Resident Hepatic Cells in a Rat Model of Liver Fibrosis

In a rat model of liver fibrosis, researchers investigated the effects of human amniotic membrane and epithelial cells (hAEC) on resident hepatic cells contributing to myofibroblast generation. hAEC reduced the activation of portal fibroblasts rather than hepatic stellate cells. [J Cell Mol Med] Full Article

PHP14 Regulates Hepatic Stellate Cells Migration in Liver Fibrosis via Mediating TGF-β1 Signaling to PI3Kγ/AKT/Rac1 Pathway

14 kDa phosphohistidine phosphatase (PHP14) expression was up-regulated in fibrotic liver and mainly in hepatic stellate cells (HSCs). PHP14 promoted HSCs migration and promoted 3D floating collagen matrices contraction but inhibited stressed-released matrices contraction. PHP14 specifically mediated the TGF-β1 signaling to PI3Kγ/AKT pathway and regulated HSC migration, and thus participated in liver fibrosis. [J Mol Med (Berl)] Abstract

PGE₂ Induces Apoptosis of Hepatic Stellate Cells and Attenuates Liver Fibrosis in Mice by Downregulating miR-23a-5p and miR-28a-5p

The authors evaluated the role of cyclooxygenase-2 (COX-2) in the regulation of a specific set of miRNAs on a mouse model of CCl₄ and bile duct ligation-induced liver fibrosis. Their results provide evidence that COX-2 represses miR-23a-5p and miR-28-5p expression in hepatic stellate cells. [Biochim Biophys Acta] Abstract

AQP3 Is Regulated by PPARγ and JNK in Hepatic Stellate Cells Carrying PNPLA3 I148M

Investigators explored the role of aquaglyceroporin (AQP) 3 for hepatic stellate cell (HSC) activation and unveiled its potential interactions with patatin-like phospholipase domain-containing 3 (PNPLA3). The PPARγ agonist, rosiglitazone, recovered AQP3 expression also in PNPLA3 I148M carrying HSCs. When PNPLA3 was silenced, AQP3 expression increased. [Sci Rep] Full Article

A Perfusion Incubator Liver Chip for 3D Cell Culture with Application on Chronic Hepatotoxicity Testing

The authors designed a perfusion-incubator-liver-chip for 3D cell culture, that assured a tangential flow of the media over the spheroids culture. Rat hepatocyte spheroids constrained between a cover glass and a porous-ultrathin Parylene C membrane experienced optimal mass transfer and limited shear stress from the flowing culture media; maintained cell viability over 24 days. [Sci Rep] Full Article

Connexin 32 and Connexin 43 Are Involved in Lineage Restriction of Hepatic Progenitor Cells to Hepatocytes

Scientists investigated the influence of connexin (Cx) 32 and Cx43 on hepatocyte differentiation of WB-F344 cells by in vitro gain and loss of function analyses. An inhibitor of Cx32 was also used to make further clarification. [Stem Cell Res Ther] Full Article

Mitogen-Activated Protein Kinase Regulation in Hepatic Metabolism

Discussion of recent insights into the mitogen-activated protein kinases (MAPK)/MAPK phosphatases (MKPs) signaling role in hepatic metabolic function and disease is the focus of this review. [Trends Endocrinol Metab] Abstract

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

Boehringer Ingelheim and MiNA Therapeutics to Develop Novel Treatment Approaches for Fibrotic Liver Diseases

Boehringer Ingelheim and MiNA Therapeutics announced that they have signed a collaboration and licensing agreement focused on the development of novel compounds to treat fibrotic liver diseases such as NASH, based on MiNA’s small activating RNA therapeutics platform. [Boehringer Ingelheim] Press Release

Dynavax Announces FDA Approval of HEPLISAV-B^™ for Prevention of Hepatitis B in Adults

Dynavax Technologies Corporation announced that the FDA has approved HEPLISAV-B for prevention of infection caused by all known subtypes of hepatitis B virus in adults age 18 years and older. HEPLISAV-B is the first new hepatitis B vaccine in the United States in more than 25 years and the only two-dose hepatitis B vaccine for adults. [Dynavax Technologies Corporation] Press Release

UK Government Appoints Next Chief Scientific Adviser

Patrick Vallance, president of research and development at the pharmaceutical giant GlaxoSmithKline, has been appointed as chief scientific adviser, the UK government announced. [Nature News] Editorial

Indian Scientists Urged to Speak Out about Pseudoscience

A leading Indian science-advocacy group is urging the country’s researchers to speak out against pseudoscience, which it fears has gained a foothold in the past few years, partly through support from some agencies of the Indian government. [Nature News] Editorial

Court Demands that Search Engines and Internet Service Providers Block Sci-Hub

The American Chemical Society (ACS) has won a lawsuit against Sci-Hub, a website providing illicit free access to millions of paywalled scientific papers. ACS had alleged copyright infringement, trademark counterfeiting and trademark infringement; a district court in Virginia ruled that Sci-Hub should pay the ACS $4.8 million in damages after Sci-Hub representatives failed to attend court. [ScienceInsider] Editorial

NEW The SHC-The Science of HBV Cure Conference 2018
June 8-9, 2018
Singapore, Singapore

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NEW Principal Scientist – Liver Disease Research (Novo Nordisk)

Postdoctoral Position – Liver Disease (University of Illinois)

Biomedical Scientist – Molecular and Cellular Gastroenterology (Mayo Clinic)

PhD Studentships – Cancer Research (Institute of Cancer Research)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

Research Assistant – Viral Hepatitis/Alcohol Group (Foundation for Liver Research)

Postdoctoral Position – 3D Organoid Mechanobiology (KU Leuven)

Postdoctoral Research Fellow – Liver Tissue Engineering (Massachusetts General Hospital)

Hepatologist – Gastroenterology and Hepatology (The Liver Institute of Virginia)

Faculty Position – Molecular Oncology (Moffitt Cancer Center)

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