Transcriptomics,Genomics

Dataset Information

32

Animal model of acute-on-chronic alcoholic liver injury


ABSTRACT: Background and aims: We aimed to study the pathogenesis of AH in an animal model of acute-on-chronic alcoholic liver disease which combines chronic hepatic fibrosis with intragastric alcohol administration. Methods: Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fibrosis. Then, ethyl alcohol (EtOH) (up to 25 g/kg/day, for 3 weeks) was administered continuously to mice via a gastric feeding tube, with or without one-half dose of CCl4. Liver and serum markers were evaluated to characterize acute-on-chronic-alcoholic liver disease in our model. Results: CCl4 or EtOH treatment alone induced liver fibrosis or steatohepatitis, respectively, findings that were consistent with expected pathology. Combined treatment with CCl4 and EtOH resulted in a marked exacerbation of liver injury, as evident by the development of hepatic inflammation, marked steatosis, and pericellular fibrosis, and by increased serum transaminase levels, compared to mice treated with either treatment alone. Liver transcriptomic changes specific to combined treatment group demonstrated close concordance with pathways perturbed in human severe cases of AH. In addition to gene expression changes, E. coli and Candida species were also significantly more abundant in livers of mice co-treated with CCl4 and EtOH. Conclusions: Mice treated with CCl4 and EtOH displayed several key characteristics of human AH, including pericellular fibrosis, increased hepatic bacterial load, and dysregulation of the same molecular pathways. This model may be useful for developing therapeutics for AH. Overall design: Animal model of acute-on-chronic alcoholic liver injury

INSTRUMENT(S): Illumina HiSeq 2500 (Mus musculus)

SUBMITTER: Ivan Rusyn  

PROVIDER: GSE119470 | GEO | 2018-09-05

REPOSITORIES: GEO

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Publications

Histopathological and Molecular Signatures of a Mouse Model of Acute-on-Chronic Alcoholic Liver Injury Demonstrate Concordance With Human Alcoholic Hepatitis.

Furuya Shinji S   Cichocki Joseph A JA   Konganti Kranti K   Dreval Kostiantyn K   Uehara Takeki T   Katou Yuuki Y   Fukushima Hisataka H   Kono Hiroshi H   Pogribny Igor P IP   Argemi Josepmaria J   Bataller Ramon R   Rusyn Ivan I  

Toxicological sciences : an official journal of the Society of Toxicology 20190801 2


Human alcoholic hepatitis (AH) carries a high mortality rate. AH is an acute-on-chronic form of liver injury characterized by hepatic steatosis, ballooned hepatocytes, neutrophil infiltration, and pericellular fibrosis. We aimed to study the pathogenesis of AH in an animal model which combines chronic hepatic fibrosis with intragastric alcohol administration. Adult male C57BL6/J mice were treated with CCl4 (0.2 ml/kg, 2×weekly by intraperitoneal injections for 6 weeks) to induce chronic liver fi  ...[more]

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