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Presentation
Roles of the primary bile acid receptor FXR in liver repair and tumorigenesis
AACR (2012)
  • Zhipeng Meng, University of California - San Diego
Abstract
Bile acids promote processing of dietary fat and regulate glucose
homeostasis in liver through its receptor, FXR. In our study, we
demonstrate that bile acid/FXR signaling also plays a role in the tissue
homeostasis and repair as well as hepatocarcinogenesis. Either decreased
bile acid level or loss of FXR leads to impaired liver regeneration after
carbon tetrachloride-induced liver injury or 70% partial hepatectomy, which
indicates that FXR is an essential liver protector by regulating liver cell
proliferation and death. Indeed, FXR-/- mice spontaneously develop liver
cancer when they are aged due to their chronic liver injury and deregulated
repair. In addition, FXR expression is down-regulated in human liver
tumors compared with non-tumor regions, and the hepatocarcinogenesis in
FXR-/- mice can recapitulate the process of human liver cancer initiation
and progression. Therefore, FXR-/- mice provide a unique animal model for
liver cancer study. For instance, we generated IFNα-/-FXR-/- mice to clarify
the tumor suppressor role of the cytokine IFNα, the function of which was
ever under debate. FXR-/- mice can be also used to identify or predict
more differentially expressed genes in human liver cancer. For example,
we found that one liver-rich miRNA, miR-194, which is down-regulated in
the liver tumors of FXR-/- mice, is an important liver epithelial cell marker
and prevents cancer metastasis, which has not been described before. In
conclusion, ablation of FXR increases susceptibility to liver injury and
tumorigenesis, and the FXR-/- mice provide a unique animal model for
human liver cancer study.
Disciplines
Publication Date
2012
Citation Information
Zhipeng Meng. "Roles of the primary bile acid receptor FXR in liver repair and tumorigenesis" AACR (2012)
Available at: http://works.bepress.com/zhipeng-meng/11/