Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor

Davies, Richard A.

doi:10.1093/carcin/bgi365

Cited by 39 publications

(26 citation statements)

References 47 publications

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“…Oval cell apoptosis has been shown to be mediated via Akt activity (Davies et al, 2006). We observed that a few oval cells stained positively for Bcl-2 and caspase 8 especially in the periportal areas.…”

Section: Brdu and Tunel Stainingmentioning

confidence: 61%

Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats

Azamai

Sulaiman

Habib

et al. 2009

J. Zhejiang Univ. Sci. B

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Chlorella vulgaris (CV) has been reported to have antioxidant and anticancer properties. We evaluated the effect of CV on apoptotic regulator protein expression in liver cancer-induced rats. Male Wistar rats (200~250 g) were divided into eight groups: control group (normal diet), CDE group (choline deficient diet supplemented with ethionine in drinking water to induce hepatocarcinogenesis), CV groups with three different doses of CV (50, 150, and 300 mg/kg body weight), and CDE groups treated with different doses of CV (50, 150, and 300 mg/kg body weight). Rats were sacrificed at various weeks and liver tissues were embedded in paraffin blocks for immunohistochemistry studies. CV, at increasing doses, decreased the expression of anti-apoptotic protein, Bcl-2, but increased the expression of pro-apoptotic protein, caspase 8, in CDE rats, which was correlated with decreased hepatoctyes proliferation and increased apoptosis as determined by bromodeoxy-uridine (BrdU) labeling and terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) assay, respectively. Our study shows that CV has definite chemopreventive effect by inducing apoptosis via decreasing the expression of Bcl-2 and increasing the expression of caspase 8 in hepatocarcinogenesis-induced rats.

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Section: Brdu and Tunel Stainingmentioning

confidence: 61%

Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats

Azamai

Sulaiman

Habib

et al. 2009

J. Zhejiang Univ. Sci. B

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“…LPCs are recognized as being highly heterogeneous and dynamic, and several previous studies from our laboratory have illustrated selective modulation of discrete subpopulations of LPCs by cytokines. 3,30,31 Because the LPC compartment induced in various liver injury models may be different, we aimed to further explore the role of the TWEAK pathway in an additional in vivo model of LPC expansion and to study its effects directly on LPC lines in vitro.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Tirnitz–Parker¹,

Viebahn²,

Jakubowski³

et al. 2010

Hepatology

160

182

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Liver progenitor cells (LPCs) represent the cell compartment facilitating hepatic regeneration during chronic injury while hepatocyte-mediated repair mechanisms are compromised. LPC proliferation is frequently observed in human chronic liver diseases such as hereditary hemochromatosis, fatty liver disease, and chronic hepatitis. In vivo studies have suggested that a tumor necrosis factor family member, tumor necrosis factor–like weak inducer of apoptosis (TWEAK), is promitotic for LPCs; whether it acts directly is not known. In our murine choline-deficient, ethionine-supplemented (CDE) model of chronic liver injury, TWEAK receptor [fibroblast growth factor-inducible 14 (Fn14)] expression in the whole liver is massively upregulated. We therefore set out to investigate whether TWEAK/Fn14 signaling promotes the regenerative response in CDE-induced chronic liver injury by mitotic stimulation of LPCs. Fn14 knockout (KO) mice showed significantly reduced LPC numbers and attenuated inflammation and cytokine production after 2 weeks of CDE feeding. The close association between LPC proliferation and activation of hepatic stellate cells in chronic liver injury prompted us to investigate whether fibrogenesis was also modulated in Fn14 KO animals. Collagen deposition and expression of key fibrogenesis mediators were reduced after 2 weeks of injury, and this correlated with LPC numbers. Furthermore, the injection of 2-week-CDE-treated wildtype animals with TWEAK led to increased proliferation of nonparenchymal pan cytokeratin–positive cells. Stimulation of an Fn14-positive LPC line with TWEAK led to nuclear factor kappa light chain enhancer of activated B cells (NFκB) activation and dose-dependent proliferation, which was diminished after targeting of the p50 NFκB subunit by RNA interference. Conclusion: TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFκB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. (Hepatology 2010)

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“…As oval cellmediated liver regeneration is accompanied by an inflammatory response, these cytokines could play an important role. Inhibiting this response, by treating with dexamethasone or a cyclooxygenase 2 inhibitor, reduces the expansion of oval cells in the damaged liver (43,44).…”

Section: Discussionmentioning

confidence: 99%

Lymphocytes Support Oval Cell-Dependent Liver Regeneration

Strick‐Marchand

Masse

Weiss

et al. 2008

The Journal of Immunology

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In case of hepatic damage, the liver uses a unique regeneration mechanism through proliferation of hepatocytes. If this process is inhibited, bipotent oval stem cells proliferate and differentiate to hepatocytes and bile ducts, thus restoring liver mass. Although oval cell accumulation in the liver is often associated with inflammatory processes, the role of lymphocytes in oval cell-mediated hepatic regeneration is poorly understood. We treated wild-type and immunodeficient mice with an oval cell-inducing diet: in the absence of T cells (CD3ε−/− and Rag2−/−) there were fewer oval cells, whereas in alymphoid mice (Rag2−/−γc−/−) a strongly reduced oval cell response and higher mortality, due to liver failure, was observed. Adoptive transfer of T cells into alymphoid mice protected them from liver failure, but was insufficient to restore the oval cell response. Treatment of Rag2−/− mice with an NK cell-depleting Ab resulted in a significantly diminished oval cell response. These genetic experiments point to a major role for NK and T cells in oval cell expansion. In wild-type mice, oval cell proliferation is accompanied by an intrahepatic inflammatory response, characterized by the recruitment of Kupffer, NK, NKT, and T cells. Under these conditions, lymphocytes produce TH1 proinflammatory cytokines (IFN-γ and TNF-α) that are mitogenic for oval cells. Our data suggest that T and NK lymphocytes stimulate oval cell expansion by local cytokine secretion. This beneficial cross-talk between the immune system and liver stem cells operates under noninfectious conditions and could promote tissue regeneration following acute liver damage.

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Hepatic oval cell response to the choline-deficient, ethionine supplemented model of murine liver injury is attenuated by the administration of a cyclo-oxygenase 2 inhibitor

Cited by 39 publications

References 47 publications

Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats

Chlorella vulgaris triggers apoptosis in hepatocarcinogenesis-induced rats

Tumor Necrosis Factor–Like Weak Inducer of Apoptosis Is a Mitogen for Liver Progenitor Cells

Lymphocytes Support Oval Cell-Dependent Liver Regeneration

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