Divergent Inflammatory, Fibrogenic, and Liver Progenitor Cell Dynamics in Two Common Mouse Models of Chronic Liver Injury

J. Köhn-Gaone, B.J. Dwyer, C.A. Grzelak, G. Miller, N.A. Shackel, G.A. Ramm, G.W. Mccaughan, Caryn L. Elsegood, J.K. Olynyk, Janina E. E. Tirnitz-Parker

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

© 2016 American Society for Investigative Pathology
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.
Original languageEnglish
Pages (from-to)1762-1774
Number of pages13
JournalAmerican Journal of Pathology
Volume186
Issue number7
Early online date13 May 2016
DOIs
Publication statusPublished - Jul 2016

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