Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice

B. Knight; B. Akhurst; V.B. Matthews; R.G. Ruddell; G.A. Ramm; L.J. Abraham; J.K. Olynyk; G.C. Yeoh

doi:10.1016/j.jhep.2006.08.015

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Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice

Journal article

Peer reviewed

Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice

B. Knight, B. Akhurst, V.B. Matthews, R.G. Ruddell, G.A. Ramm, L.J. Abraham, J.K. Olynyk and G.C. Yeoh

Journal of Hepatology, Vol.46(1), pp.134-141

2007

DOI: https://doi.org/10.1016/j.jhep.2006.08.015

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Abstract

Background/Aims Liver regeneration following chronic injury is associated with inflammation, the proliferation of liver progenitor (oval) cells and fibrosis. Previous studies identified interferon-gamma as a key mediator of oval cell proliferation. Interferon-γ is known to regulate Th1 cell activities during immune challenge. Therefore, we hypothesised that progenitor cell-mediated regeneration is associated with a Th1 immune response. Methods C57Bl/6 (normal Th1 response) and BALB/c mice (deficient in Th1 signalling) were placed on a carcinogenic diet to induce liver injury, progenitor cell proliferation and fibrosis. Results Serum transaminases and mortality were elevated in BALB/c mice fed the diet. Proliferation of liver progenitor cells was significantly attenuated in BALB/c animals. The pattern of cytokine expression and inflammation differed between strains. Liver fibrosis and hepatic stellate cell activation were significantly inhibited in BALB/c mice compared to C57Bl/6. In addition, interferon-γ knockout mice also showed reduced fibrosis compared to wild type. These findings are in contrast to published results, in which interferon-gamma is shown to be anti-fibrogenic. Conclusions Our data demonstrate that the hepatic progenitor cell response to a CDE diet is inhibited in mice lacking Th1 immune signalling and further show that this inhibition is associated with reduced liver fibrosis.

Details

Title: Attenuated liver progenitor (oval) cell and fibrogenic responses to the choline deficient, ethionine supplemented diet in the BALB/c inbred strain of mice
Authors/Creators: B. Knight (Author/Creator) - Fremantle Hospital
B. Akhurst (Author/Creator) - The University of Western Australia
V.B. Matthews (Author/Creator)
R.G. Ruddell (Author/Creator) - QIMR Berghofer Medical Research Institute
G.A. Ramm (Author/Creator) - QIMR Berghofer Medical Research Institute
L.J. Abraham (Author/Creator) - The University of Western Australia
J.K. Olynyk (Author/Creator) - Fremantle Hospital
G.C. Yeoh (Author/Creator) - The University of Western Australia
Publication Details: Journal of Hepatology, Vol.46(1), pp.134-141
Publisher: Elsevier
Identifiers: 991005543721807891
Copyright: 2006 European Association for the Study of the Liver
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Citation topics: 1 Clinical & Life Sciences; 1.102 Stem Cell Research; 1.102.1150 Hepatocyte Growth Factor
Web Of Science research areas: Gastroenterology & Hepatology
ESI research areas: Clinical Medicine