A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer

Autor: Maria D. Ybanez, M. Isabel Fiel, Nicolas Goossens, Youngmin A. Lee, Sebastiao Martins, Hsin I. Chou, Naoto Fujiwara, Yujin Hoshida, Takuma Tsuchida, Scott L. Friedman, Brittany Allen
Přispěvatelé: Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Mitsubishi Tanabe Pharma Corporation [Saitama, Japan], Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Departamento de Patologia [São Paulo, SP, Brazil] (Faculdade de Medicina FMUSP), Universidade de São Paulo = University of São Paulo (USP), Department of Pathology [New York, NY, USA], YH is supported by NIH/NIDDK DK099558, European Commission ERC-2014-AdG-671231, Irma T. Hirschl Trust, US Department of Defense W81XWH-16-1-0363. SLF is supported by NIH DK56621 and the US Department of Defense CA150272 and NIH1P30 CA 196521-01. YAL is supported in part by grant # UL1TR001866 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program., European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016), daulny, anne, Cell circuits as targets and biomarkers for liver disease and cancer prevention - HEPCIR - - H20202016-01-01 - 2020-12-31 - 671231 - VALID, Research Division [Saitama, Japan], Universidade de São Paulo (USP)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Liver Cirrhosis
0301 basic medicine
Cirrhosis
Hepatocellular carcinoma
digestive system
Article
03 medical and health sciences
Mice
Fibrosis
Non-alcoholic Fatty Liver Disease
Hepatic stellate cells
NAFLD
medicine
Animals
Carbon Tetrachloride
Steatohepatitis
Inflammation
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Hepatology
Fatty liver disease models
business.industry
Gene Expression Profiling
Fatty liver
Liver Neoplasms
NASH
Reproducibility of Results
Cancer
Insulin resistance
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
medicine.disease
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
digestive system diseases
3. Good health
Diet
Fatty Liver
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Diet
Western
Disease Progression
Cancer research
Steatosis
Liver cancer
business
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Journal of Hepatology
Journal of Hepatology, Elsevier, 2018, 69 (2), pp.385-395. ⟨10.1016/j.jhep.2018.03.011⟩
ISSN: 0168-8278
1600-0641
DOI: 10.1016/j.jhep.2018.03.011⟩
Popis: Yujin Hoshida and Scott L. Friedman contributed equally and are co-senior authors.Erratum in Corrigendum to "A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer" [J Hepatol 69 (2018) 385-395]. [J Hepatol. 2018].Comment in Towards a definite mouse model of NAFLD. [J Hepatol. 2018]; International audience; BACKGROUND AND AIMS:Although the majority of patients with non-alcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizeable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming.METHODS:We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low weekly dose of intraperitoneal carbon tetrachloride (CCl4), which serves as an accelerator.RESULTS:C57BL/6J mice were fed a normal chow diet ± CCl4 or WD ± CCl4 for 12 and 24 weeks. Addition of CCl4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl4 mice and immunologic features were similar to those of human NASH.CONCLUSIONS:Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing.LAY SUMMARY:A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model make it ideal to study disease pathogenesis and test new treatments.
Databáze: OpenAIRE
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