Transcriptomic analysis of a mouse model of Acetaminophen-induced hepatitis

Acetaminophen (APAP) is a widely used analgesic and antipyretic drug recognized as one of the major causes of liver disease. While safe at recommend doses, APAP overdose might cause acute liver failure, representing the first cause for liver transplantation in several Western countries. GPBAR1, also known as TGR5, is a steroid-activated G protein-coupled receptor (GPCRs), activated by secondary bile acids. GPBAR1 is not expressed by hepatocytes, but is highly represented by Kupffer cells, monocytes and macrophages, NKT cells and liver sinusoidal cells. Previous studies have shown that GPBAR1 activation regulates these cells of innate immunity, contributing to maintenance of a tolerogenic state by intestinal and liver macrophages. Here, we investigated the role of GPBAR1 in a mouse model of APAP-induced hepatitis. To gain insights on the pathogenesis and on the therapeutic role of GPBAR1 agonism in this model, mice were administered with APAP (500 mg/kg), alone or in combination with a GPBAR1 agonist, known as BAR501 (30 mg/kg). Total RNA extracted from the livers of each group of mice were subjected to RNAseq analysis performed on Ion S5 Sequencer with Torrent Suite Software v6.