Maeso-Díaz, Raquel; Boyer-Diaz, Zoe; Lozano, Juan José; Ortega-Ribera, Martí; Peralta, Carmen; Bosch, Jaime; Gracia-Sancho, Jordi (2019). New Rat Model of Advanced NASH Mimicking Pathophysiological Features and Transcriptomic Signature of The Human Disease. Cells, 8(9) MDPI 10.3390/cells8091062
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Non-alcoholic steatohepatitis (NASH) is a major cause of chronic liver disease. However, most available animal models fail to reflect the whole spectrum of the disease. Liver fibrosis and portal hypertension are the strongest prognostic markers in advanced NASH. We herein aimed at developing a new model of NASH in male rats, obtained using a multi-hit protocol that combines the administration of a high fat and high-cholesterol diet with CCl4 and phenobarbital. Following this protocol, rats showed the full characteristics of advanced human NASH after 10 weeks and NASH with cirrhosis by 24 weeks. Specifically, our NASH rats exhibited: steatosis and metabolic syndrome, lipotoxicity, hepatocellular ballooning necrosis, inflammation and importantly, marked hepatic fibrosis and significant portal hypertension. Furthermore, a whole transcriptomic analysis of liver tissue from our rat model using next generation sequencing was compared with human NASH and illustrated the similarity of this pre-clinical model with the human disease. Pathway enrichment analysis showed that NASH animals shared a relevant number of central pathways involved in NASH pathophysiology, such as those related with cell death, as well as inflammatory or matrix remodeling. The present study defines a pre-clinical model of moderate and advanced NASH that mimics the human disease, including pathophysiologic characteristics and transcriptomic signature.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) |
UniBE Contributor: |
Bosch Genover, Jaime, Gracia Sancho, Jorge Sergio |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2073-4409 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Thi Thao Anh Pham |
Date Deposited: |
08 Jan 2020 10:22 |
Last Modified: |
02 Mar 2023 23:32 |
Publisher DOI: |
10.3390/cells8091062 |
PubMed ID: |
31510105 |
Uncontrolled Keywords: |
cirrhosis hepatic fibrosis portal hypertension steatohepatitis steatosis |
BORIS DOI: |
10.7892/boris.137287 |
URI: |
https://boris.unibe.ch/id/eprint/137287 |
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