Roles of the primary bile acid receptor FXR in liver repair and tumorigenesisAACR (2012)
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.
Citation InformationZhipeng Meng. "Roles of the primary bile acid receptor FXR in liver repair and tumorigenesis" AACR (2012)
Available at: http://works.bepress.com/zhipeng-meng/13/