Fas-Mediated Apoptosis in Primary Cultured Mouse Hepatocytes

Ni, Runzhou; Tomita, Yumiko; Matsuda, Koichi; Ichihara, Akira; Ishimura, Kazunori; Ogasawara, Jun; Nagata, Shinji

doi:10.1006/excr.1994.1349

Cited by 189 publications

(134 citation statements)

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“…16 Moreover, FasL treatment in combination with the transcriptional inhibitor ActD induces death of adult hepatocytes. 28 We first tested whether fas is expressed in embryonic livers by reverse transcription PCR. Low levels of fas expression were detected at E13 (Fig.…”

Section: Hgf Prevents Fas-induced Cell Death Andmentioning

confidence: 99%

Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner

et al. 2007

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Section: Hgf Prevents Fas-induced Cell Death Andmentioning

confidence: 99%

Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner

et al. 2007

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“…It has been described that hepatocytes exposed to antiFas antibodies (Jo2) efficiently undergo apoptosis in the presence of actinomycin D (15,18,42). Hepatocytes were pretreated with different concentrations of AR for 3 h prior to actinomycin D and Jo2 antibody addition.…”

Section: Expression Of Egf-r Ligands In Mouse Liver After the Adminismentioning

confidence: 99%

Novel Role for Amphiregulin in Protection from Liver Injury

Berasain

Garcı́a-Trevijano

Castillo

et al. 2005

Journal of Biological Chemistry

119

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Clinically, the Fas and Fas ligand system plays a central role in the development of hepatocyte apoptosis, a process contributing to a broad spectrum of liver diseases. Therefore, the development of therapies aimed at the inhibition of hepatocyte apoptosis is a major issue. Activation of the epidermal growth factor receptor has been shown to convey survival signals to the hepatocyte. To learn about the endogenous response of epidermal growth factor receptor ligands during Fas-mediated liver injury we investigated the expression of epidermal growth factor, transforming growth factor ␣, heparinbinding epidermal growth factor-like growth factor, betacellulin, epiregulin, and amphiregulin in the liver of mice challenged with Fas-agonist antibody. Amphiregulin expression, barely detectable in healthy liver, was significantly up-regulated. Amphiregulin administration abrogated Fas-mediated liver injury in mice and showed direct anti-apoptotic effects in primary hepatocytes. Amphiregulin activated the Akt and signal transducer and activator of transcription-3 survival pathways, and up-regulated Bcl-xL expression. Amphiregulin knock-out mice showed signs of chronic liver damage in the absence of any noxious treatment, and died faster than wild type mice in response to lethal doses of Fas-agonist antibody. In contrast, these mice were more resistant against sublethal liver damage, supporting the hypothesis that chronic liver injury can precondition hepatocytes inducing resistance to subsequent cell death. These results show that amphiregulin is a protective factor induced in response to liver damage and that it may be therapeutic in liver diseases.

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“…Previous studies have been performed in primary hepatocyte cultures [33][34][35] rather than freshly isolated hepatocytes. Although the same strain of mouse was used as hepatocyte donors, the cells maintained in culture were nearly completely refractory to anti-Fas-induced apoptosis unless inhibitors of protein synthesis (cycloheximide) or protein kinase C (H7) were present.…”

Section: Apoptosis In Freshly Isolated Hepatocytes Through Fas Antigenmentioning

confidence: 99%

“…27,[33][34][35][36] However, cultured cells are very refractory to anti-Fas antibody treatment as compared with the in vivo situation in which full destruction of the liver occurs within a few hours. In contrast, as reported here, hepatocytes freshly isolated from mice remain highly responsive to Fas antigen stimulation, and nearly the entire cell population becomes apoptotic within a few hours of stimulation by anti-Fas antibody.…”

mentioning

confidence: 99%