Hepatic Cell News Volume 4.17 | May 15 2020

TOP STORY

Hepatic Stellate Cell Autophagy Inhibits Extracellular Vesicle Release to Attenuate Liver Fibrosis

The effect of autophagy in regulating fibrogenic extracellular vesicles (EVs) and amplifying pro-fibrotic signals among hepatic stellate cells (HSCs) remains unknown. Scientists aimed to understand the role of autophagy in HSC-derived fibrogenic EV release in liver fibrosis. [J Hepatol] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Hepatocyte Mitochondria-Derived Danger Signals Directly Activate Hepatic Stellate Cells and Drive Progression of Liver Fibrosis

Using liver fibrosis resistant/susceptible mouse strain system, the authors demonstrated that mito-DAMPs released from injured hepatocyte mitochondria directly activate hepatic stellate cells, the fibrogenic cell in the liver, and drive liver scarring. [Nat Commun] Full Article

TMEM9‐v‐ATPase Activates Wnt/β‐Catenin Signaling via APC Lysosomal Degradation for Liver Regeneration and Tumorigenesis

Transmembrane protein 9 (TMEM9) was highly expressed in regenerating liver and hepatocellular carcinoma cells. TMEM9 expression was enriched in the hepatocytes around the central vein and acutely induced by injury. [Hepatology] Abstract

Attenuation of the Heparan Sulfate Proteoglycan Binding Enhances In Vivo Transduction of Human Primary Hepatocytes with AAV2

Scientists determined that just two of the eleven changes present in AAV-NP59 account for the enhanced transduction performance of a capsid variant in primary human hepatocytes in vivo, an effect that they have associated with attenuation of heparan sulfate proteoglycan binding affinity. [Mol Ther Methods Clin Dev] Abstract | Graphical Abstract

SOX4 Activates CXCL12 in Hepatocellular Carcinoma Cells to Modulate Endothelial Cell Migration and Angiogenesis In Vivo

The CXCL12 promoter was activated by ectopic expression of a Flag-tagged SOX4 plasmid, endogenous SOX4 knockdown abolished promoter activity of CXCL12 as shown by luciferase assays, and an association with the CXCL12 promoter was identified via chromatin immunoprecipitation in hepatocellular carcinoma cells. [Oncogene] Abstract

CircZNF609 Enhances Hepatocellular Carcinoma Cell Proliferation, Metastasis, and Stemness by Activating the Hedgehog Pathway through the Regulation of miR-15a-5p/15b-5p and GLI2 Expressions

CircZNF609 was conspicuously overexpressed and featured with loop structure in hepatocellular carcinoma (HCC). Functional tests revealed that decreased expression of circZNF609 suppressed cell proliferation, metastasis and stemness, whereas induced cell apoptosis in HCC. [Cell Death Dis] Full Article

The Novel miR-1269b-Regulated Protein SVEP1 Induces Hepatocellular Carcinoma Proliferation and Metastasis Likely through the PI3K/Akt Pathway

Downregulation of SVEP1 expression promoted in vitro hepatocellular carcinoma cell migration, chemotaxis, invasion and proliferation, as well as in vivo tumor growth, local invasion and metastasis in a mouse model. [Cell Death Dis] Full Article

Human Multi-Organ Chip Co-Culture of Bronchial Lung Culture and Liver Spheroids for Substance Exposure Studies

Researchers co-cultured a human lung equivalent from the commercially available bronchial MucilAir culture and human liver spheroids from HepaRG cells to assess the potential toxicity of inhaled substances under conditions that permit organ crosstalk. [Sci Rep] Full Article

miR-155 Accelerates the Growth of Human Liver Cancer Cells by Activating CDK2 via Targeting H3F3A

Investigators indicated that abnormal miR-155 was negatively correlated with the expression of P21WAF1/Cip1. They suggest that miR155 alters the transcriptome and inhibits the expression of H3F3A in liver cancer cells. [Mol Ther Oncolytics] Abstract | Graphical Abstract

Antineoplastic Activity of a Novel Ruthenium Complex against Human Hepatocellular Carcinoma (HepG2) and Human Cervical Adenocarcinoma (HeLa) Cells

Investigators evaluated the cytotoxic effects of a ruthenium complex, namely cis-[Ru(1,10-phenanthroline)₂(imidazole)₂]²⁺, on HepG2 and HeLa cells and analyzed metabolic parameters. [Heliyon] Abstract

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The Underlying Mechanisms of Non-Coding RNAs in the Chemoresistance of Hepatocellular Carcinoma

Scientists summarize recent findings on the molecular mechanisms by which non-coding RNAs regulate hepatocellular carcinoma (HCC) chemoresistance, as well as their potential clinical implications in overcoming HCC chemoresistance. [Mol Ther Nucleic Acids] Abstract

Cell-in-Cell Structures in the Liver: A Tale of Four E’s

The authors bring together the latest reports on four types of endocytosis in the liver -efferocytosis, entosis, emperipolesis and enclysis, with a focus on hepatocyte biology. [Front Immunol] Abstract

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Ultragenyx Announces Positive Data from Confirmatory Cohort of Phase I/II Study of DTX401 Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa)

Ultragenyx Pharmaceutical Inc. announced positive initial data from the confirmatory third cohort and longer-term data from the first two cohorts of the ongoing Phase I/II study of DTX401, an adeno-associated virus based gene therapy for the treatment of GSDIa. [Ultragenyx Pharmaceutical Inc.] Press Release

Ultragenyx Announces Positive Longer-Term Results from First Three Cohorts of Phase I/II Study of DTX301 Gene Therapy in Ornithine Transcarbamylase (OTC) Deficiency

Ultragenyx Pharmaceutical Inc. announced positive longer-term safety and efficacy data from the first three cohorts of the ongoing Phase I/II study of DTX301, an investigational adeno-associated virus gene therapy for the treatment of OTC deficiency. [Ultragenyx Pharmaceutical Inc.] Press Release

Publishers Launch Joint Effort to Tackle Altered Images in Research Papers

The world’s largest science publishers are teaming up to discuss how to automatically flag altered or duplicated images in research papers. A new working group – the first formal cross-industry initiative to discuss the issue – aims to set standards for software that screens papers for problematic images during peer review. [Nature News] Editorial

House Democrats Include Research Dollars in Latest Pandemic Relief Package

For US scientists, the good news is that the $3 trillion spending bill unveiled contains billions of dollars in new research funding. The bad news is that the bill is only a marker for negotiations with Senate Republicans and the White House on what more the federal government should do to help the country deal with the devastating economic and health effects of the pandemic. [ScienceInsider] Editorial

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NEW Postdoctoral Fellowships – Liver Research (The University of Hong Kong)

Postdoctoral Scientist – Quantitative Biology (Texas Biomedical Research Institute)

Research Scientist – Liver (Spark Therapeutics)

Staff Fellow – Viral Vaccines (FDA-Center for Biologics Evaluation and Research)

Postdoctoral Fellow – Translational Cancer Research (University of New Mexico Comprehensive Cancer Center)

Postdoctoral Fellow – Molecular Diagnostics and Experimental Therapeutics (City of Hope)

Professorship of Hepatology (Ludwig-Maximilians-Universität)

Scientist – Molecular & Cellular Biology (Deep Genomics, Inc.)

Postdoctoral Position – Gut-Liver Axis (University of California, Davis)

Therapuetic Specialist – Inflammation (Gilead Sciences Inc.)

Team Leader – Cholangiocytes (Miromatrix Medical)

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