Open Access

Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis

  • Authors:
    • Fan Lian
    • Yu Wang
    • Youjun Xiao
    • Xiwen Wu
    • Hanshi Xu
    • Liuqin Liang
    • Xiuyan Yang
  • View Affiliations

  • Published online on: July 31, 2015     https://doi.org/10.3892/mmr.2015.4159
  • Pages: 5821-5827
  • Copyright: © Lian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with interface hepatitis, the presence of autoantibodies, regulatory T‑cell dysfunction and raised plasma liver enzyme levels. The present study assessed the hepatoprotective and antiapoptotic role of farnesoid X receptor (FXR) in AIH. a mouse model of AIH was induced by treatment with concanavalin A (ConA). The FXR agonist, chenodeoxycholic acid (CDCA), was administered to mice exhibiting ConA‑induced liver injury and a normal control. Blood samples were obtained to detect the levels of aminotransferases and inflammatory cytokines. Liver specimens were collected, and hematoxylin‑eosin staining was used for histopathological examination and detection. Apoptosis was evaluated using the terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling (TUNEL) method. The expression levels of apoptosis‑associated genes and proteins were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that FXR was downregulated at the mRNA and protein level in the liver specimens of mice induced with ConA‑induced hepatitis. Increased levels of aminotransferases and inflammatory cytokines, including interferon‑γ, tumor necrosis factor‑α, interleukin (IL)‑4 and IL‑2, were detected in ConA‑treated mice. The mice pretreated with the FXR agonist, CDCA, were more resistant to ConA hepatitis, as indicated by reduced levels of alanine transaminase/aspartate aminotransferase and aminotransferases. The activation of FXR ameliorated hepatocyte apoptosis, as demonstrated by TUNEL analysis and downregulation of the Fas/Fas ligand, tumor necrosis factor‑related apoptosis‑inducing ligand and caspase‑3. Taken together, FXR activation ameliorated liver injury and suppressed inflammatory cytokines in ConA‑induced hepatitis. FXR, therefore, exerts a protective role against ConA-induced apoptosis.
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October-2015
Volume 12 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Copy and paste a formatted citation
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Spandidos Publications style
Lian F, Wang Y, Xiao Y, Wu X, Xu H, Liang L and Yang X: Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis. Mol Med Rep 12: 5821-5827, 2015
APA
Lian, F., Wang, Y., Xiao, Y., Wu, X., Xu, H., Liang, L., & Yang, X. (2015). Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis. Molecular Medicine Reports, 12, 5821-5827. https://doi.org/10.3892/mmr.2015.4159
MLA
Lian, F., Wang, Y., Xiao, Y., Wu, X., Xu, H., Liang, L., Yang, X."Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis". Molecular Medicine Reports 12.4 (2015): 5821-5827.
Chicago
Lian, F., Wang, Y., Xiao, Y., Wu, X., Xu, H., Liang, L., Yang, X."Activated farnesoid X receptor attenuates apoptosis and liver injury in autoimmune hepatitis". Molecular Medicine Reports 12, no. 4 (2015): 5821-5827. https://doi.org/10.3892/mmr.2015.4159