Hepatic Cell News Volume 1.09 | Mar 24 2017

TOP STORY

Regulation of Hepatic Lipogenesis by the Zinc Finger Protein Zbtb20

Investigators demonstrated that the zinc finger protein Zbtb20 is required for de novo lipogenesis. Mice lacking Zbtb20 in the liver exhibited hypolipidemia and reduced levels of liver triglycerides, along with impaired hepatic lipogenesis. They showed that Zbtb20 ablation protects from diet-induced liver steatosis and improves hepatic insulin resistance. [Nat Commun] Full Article

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Hepatic FcRn Regulates Albumin Homeostasis and Susceptibility to Liver Injury

Scientists demonstrated that mice with global or liver-specific neonatal crystallizable fragment receptor (FcRn) deletion exhibit hypoalbuminemia, albumin loss into the bile, and increased albumin levels in the hepatocyte. In vitro models with polarized cells illustrated that FcRn mediates basal recycling and bidirectional transcytosis of albumin and uniquely determined the physiologic release of newly synthesized albumin into the basal milieu. [Proc Natl Acad Sci USA] Full Article

Focal Adhesion Kinase Depletion Reduces Human Hepatocellular Carcinoma Growth by Repressing Enhancer of Zeste Homolog 2

The authors found that focal adhesion tyrosine kinase (FAK) depletion in hepatocellular carcinoma (HCC) cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes. Among these genes, they showed that FAK silencing decreased transcription and nuclear localization of enhancer of zeste homolog 2 and its tri-methylation activity on lysine 27 of histone H3. [Cell Death Differ] Full Article

CCDC178 Promotes Hepatocellular Carcinoma Metastasis through Modulation of Anoikis

Researchers found that coiled-coil domain-containing protein 178 (CCDC178) is upregulated in hepatocellular carcinoma (HCC) tissues and its overexpression is correlated with pathological stage. CCDC178 deficiency reduced the anchorage-independent growth and anoikis resistance of HCC cells, and inhibited the HCC metastasis in vivo. [Oncogene] Abstract

Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

To examine the possibility of using organoids to model steatosis, investigators established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Lipid accumulation was observed in all organoids and feline liver organoids accumulated more lipid droplets than human organoids. [Stem Cell Reports] Full Article

NPAS2 Promotes Cell Survival of Hepatocellular Carcinoma by Transactivating CDC25A

The authors investigated the expression of neuronal PAS domain protein 2 (NPAS2) and its clinical significance in hepatocellular carcinoma (HCC). They then systematically explored the role of NPAS2 in HCC cell survival both in vitro and in vivo and the underlying mechanism. NPAS2 was frequently upregulated in HCC, which significantly facilitated cell survival both in vitro and in vivo mainly by promoting cell proliferation and inhibiting mitochondria-dependent intrinsic apoptosis, and thus contributed to poor prognosis of HCC patients. [Cell Death Dis] Full Article

Hydrogen Sulfide Promotes Autophagy of Hepatocellular Carcinoma Cells through the PI3K/Akt/mTOR Signaling Pathway

Scientists investigated the effects of hydrogen sulfide on the cell biological functions of hepatocellular carcinoma. Treatment with NaHS upregulated expression of LC3-II and Atg5, two autophagy-related proteins, in HepG2 and HLE cells. [Cell Death Dis] Full Article

Egg Antigen p40 of Schistosoma japonicum Promotes Senescence in Activated Hepatic Stellate Cells via SKP2/P27 Signaling Pathway

The authors explored whether there are other signaling pathways in the process of S. japonicum egg antigen p40 (Sjp40)-induced hepatic stellate cells aging and the underlying effect of SKP2/P27 signal pathway in this procedure. They observed the Sjp40-induced decrease of α-SMA and the senescence of LX-2 cells. Sjp40 upregulated P27 and downregulated the protein level of SKP2. [Sci Rep] Full Article

Venom from Cuban Blue Scorpion Has Tumor Activating Effect in Hepatocellular Carcinoma

Scientists analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. They found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. [Sci Rep] Full Article

2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Induces Hepatic Stellate Cell (HSC) Activation and Liver Fibrosis in C57BL6 Mouse via Activating Akt and NF-κB Signaling Pathways

Researchers established an animal model of TCDD exposure by intraperitoneal injection of TCDD in male C57BL/6J mice. As revealed by Sirius red staining and hematoxylin-eosin staining evaluation, they found that TCDD-exposed mice showed extensive disruption of liver architecture, including hepatocellular necrosis, inflammatory cell infiltration, and fibrosis. [Toxicol Lett] Abstract

Liver Macrophages in Tissue Homeostasis and Disease

The authors highlight novel findings regarding the origin, classification and function of hepatic macrophages, and they discuss their divergent roles in the healthy and diseased liver. [Nat Rev Immunol] Abstract

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

Prime Therapeutics Study Finds 97 Percent of Hepatitis C Patients Cured with Harvoni^® Treatment

Nearly all patients who completed at least eight weeks of hepatitis C treatment with Gilead’s Harvoni^® were cured of the disease, according to Prime Therapeutics LLC. The results are similar to clinical trial data on the treatment, which found cure rates of 94 to 99 percent. [Press release from Prime Therapeutics LLC discussing research to be presented at the Academy of Managed Care Pharmacy’s 2017 Annual Meeting, Denver] Press Release

Aprea Therapeutics Announces Research Collaboration with Memorial Sloan Kettering Cancer Center

Aprea Therapeutics announced a collaboration with Memorial Sloan Kettering Cancer Center to study the effects of reactivation of tumor suppressor protein p53 by APR-246. The goal of the collaboration is to evaluate and characterize preclinical efficacy of APR-246 in combination with multiple other anti-cancer agents and across multiple tumor types. [Aprea Therapeutics] Press Release

SCIEX and the Children’s Medical Research Institute Announce Opening of ProCan to Advance Precision Medicine

SCIEX has announced that Children’s Medical Research Institute has opened ProCan^™, the Australian Cancer Research Foundation International Centre for the Proteome of Human Cancer. The center has been set up through an alliance with SCIEX and will enable large-scale proteome studies that will advance cancer research and ultimately aid in the promise of precision medicine. [SCIEX] Press Release

Gates Foundation Announces Open-Access Publishing Venture

The Bill & Melinda Gates Foundation is set to launch its own open-access publishing venture later this year. The initiative, Gates Open Research, will be modeled on a service begun last year by the London-based biomedical charity, the Wellcome Trust. Like that effort, the Gates Foundation’s platform is intended to accelerate the publication of articles and data from research funded by the charity. [Nature News] Editorial

Canada Budget Falls Flat with Scientists

The budget that Canadian Prime Minister Justin Trudeau’s government released lives up to his promises to emphasize innovation, and to encourage links between industry and academia. But it also presents scientists with a depressing, and unexpected, freeze on the main funding streams for basic research. [Nature News] Editorial

NEW Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
May 21-26, 2017
West Palm Beach, United States

NEW Cell Culture World Congress
May 23-24, 2017
San Diego, United States

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

NEW Principal Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

NEW Postdoctoral Position – Alcoholic Liver Fibrosis (University of Copenhagen)

NEW PhD Position – MicrobLiver (KU Leuven)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University)

Non-Tenure Track Professor – Regenerative Medicine (University of Hong Kong – Karolinska Institute Collaboration)

PhD-Candidate – Non-Alcoholic Steatohepatitis (Maastricht University)

Research Fellow – Hepatocytes (National University of Singapore)

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

Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

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