Extracellular ATP and Purinergic P2Y Receptor Signaling Promote Liver Tumorigenesis in Mice by Exacerbating DNA Damage.

Release of ATP to the extracellular compartment and subsequent activation of purinergic receptors is a conserved mechanism mediating inflammatory responses and cell fate decisions in various organs including the liver. Previous findings suggest that extracellular ATP may promote liver tumorigenesis, however, the underlying mechanisms are poorly understood. Therefore, our aim was to dissect the functions of extracellular ATP and P2Y receptors (P2YR) during hepatocarcinogenesis.

The transcription factor c-Jun/AP-1 promotes liver fibrosis during non-alcoholic steatohepatitis by regulating Osteopontin expression.

Progression of non-alcoholic fatty liver disease (NAFLD) from steatosis to non-alcoholic steatohepatitis (NASH) is a key step of NASH pathogenesis. The AP-1 transcription factor c-Jun is an important regulator of hepatic stress responses, but its contribution to NASH pathogenesis remains poorly defined. We therefore addressed c-Jun expression in liver biopsies of patients with steatosis and NASH.

Purinergic P2Y₂ receptors promote neutrophil infiltration and hepatocyte death in mice with acute liver injury.

Background & Aims: During progression of liver disease, inflammation affects survival of hepatocytes. Endogenous release of adenosine triphosphate (ATP) in the liver activates purinergic P2 receptors (P2R), which regulate inflammatory responses, but little is known about the roles of these processes in the development of acute hepatitis.

Methods: We induced acute hepatitis in C57BL/6 mice by intravenous injection of concanavalin A and then analyzed liver concentrations of ATP and expression of P2R.

Translation of stable hepadnaviral mRNA cleavage fragments induced by the action of phosphorothioate-modified antisense oligodeoxynucleotides.

Phosphorothioate-modified antisense oligodeoxynucleotides (ASOs) are used to suppress gene expression by inducing RNase H-mediated cleavage with subsequent degradation of the target mRNA. However, previous observations suggest that ASO/RNase H can also result in the generation of stable mRNA cleavage fragments and expression of truncated proteins. Here, we addressed the underlying translational mechanisms in more detail using hepadnavirus-transfected hepatoma cells as a model system of antisense therapy.

DDB treatment of patients with chronic hepatitis.

We report 13 patients (10 with chronic hepatitis C, 1 with chronic hepatitis B, 2 with nonalcoholic steatohepatitis) with persistently elevated alanine aminotransferase (ALT) levels who were treated with dimethyl-4,4'-dimethoxy-5,6,5',6-dimethylenedioxybiphenyl-2,2' dicarboxylate (DDB). ALT rapidly normalized in 12/13 patients and remained normal during treatment. Unlike ALT levels, aspartate aminotransferase, gamma-glutamyl transferase and glutamate dehydrogenase levels were not affected.