Divergent inflammatory, fibrogenic, and liver progenitor cell dynamics in two common mouse models of chronic liver injury

Kohn-Gaone, Julia, Dwyer, Benjamin J., Grzelak, Candice A., Miller, Gregory, Shackel, Nicholas A., Ramm, Grant A., McCaughan, Geoffrey W., Elsegood, Caryn L., Olynyk, John K. and Tirnitz-Parker, Janina E. E. (2016) Divergent inflammatory, fibrogenic, and liver progenitor cell dynamics in two common mouse models of chronic liver injury. American Journal of Pathology, 186 7: 1762-1774. doi:10.1016/j.ajpath.2016.03.005


Author Kohn-Gaone, Julia
Dwyer, Benjamin J.
Grzelak, Candice A.
Miller, Gregory
Shackel, Nicholas A.
Ramm, Grant A.
McCaughan, Geoffrey W.
Elsegood, Caryn L.
Olynyk, John K.
Tirnitz-Parker, Janina E. E.
Title Divergent inflammatory, fibrogenic, and liver progenitor cell dynamics in two common mouse models of chronic liver injury
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
1525-2191
Publication date 2016-07
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.ajpath.2016.03.005
Open Access Status Not Open Access
Volume 186
Issue 7
Start page 1762
End page 1774
Total pages 13
Place of publication New York, NY, United States
Publisher Elsevier
Collection year 2017
Language eng
Abstract Complications of end-stage chronic liver disease signify a major cause of mortality worldwide. Irrespective of the underlying cause, most chronic liver diseases are characterized by hepatocellular necrosis, inflammation, fibrosis, and proliferation of liver progenitor cells or ductular reactions. Vast differences exist between experimental models that mimic these processes, and their identification is fundamental for translational research. We compared two common murine models of chronic liver disease: the choline-deficient, ethionine-supplemented (CDE) diet versus thioacetamide (TAA) supplementation. Markers of liver injury, including serum alanine transaminase levels, apoptosis, hepatic fat loading, and oxidative stress, as well as inflammatory, fibrogenic and liver progenitor cell responses, were assessed at days 3, 7, 14, 21, and 42. This study revealed remarkable differences between the models. It identified periportal injury and fibrosis with an early peak and slow normalization of all parameters in the CDE regimen, whereas TAA-treated mice had pericentral patterns of progressive injury and fibrosis, resulting in a more severe hepatic injury phenotype. This study is the first to resolve two different patterns of injury and fibrosis in the CDE and TAA model and to indisputably identify the fibrosis pattern in the TAA model as driven from the pericentral vein region. Our data provide a valuable foundation for future work using the CDE and TAA regimens to model a variety of human chronic liver diseases.
Keyword Chronic liver diseases (CLDs)
Hepatocellular carcinoma (HCC)
Inflammation
Fibrosis
Proliferation of liver progenitor cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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