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Roles of the primary bile acid receptor FXR in liver repair and tumorigenesis
AACR (2012)
  • Zhipeng Meng, University of California - San Diego
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 study1-10.
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Zhipeng Meng. "Roles of the primary bile acid receptor FXR in liver repair and tumorigenesis" AACR (2012)
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