Liver regeneration after partial hepatectomy (PH) or living donor liver transplantation (LDLT) is a complicated biological process, which is not only regulated by liver itself but also by other organs through endocrine pathways. Previous studies have demonstrated that fibroblast growth factor (FGF) 15/19, which is derived from ileum, promotes hepatocellular carcinoma progression and regulates hepatic lipid metabolism. However, the role of FGF15/19 after PH is still unclear. Here, we showed that both FGF15 and hepatic phosphor- FGFR4 were high expression after PH in mice, and FGF15/19 promoted cell cycle progression, enhanced proliferation of hepatocytes and reduced hepatic lipid accumulation in vitro and in vivio.

Furthermore, applying FGFR4 knock down model with RNA interference, we showed that the effects of FGF15/FGF19 was dependent on hepatic FGFR4 which contributed to the pro-proliferative activity and regulatory lipid metabolism. In addition, the FGF15/FGF19 – FGFR4 signal transduction in hepatocyte proliferation was extracellular regulated protein kinases 1/2 dependent.

In summary, these results demonstrate that ileal FGF15/19 to hepatocyte FGFR4 axis was activated and promotes liver regeneration after PH in mice. These findings suggest that ileal FGF15/19 to hepatocyte FGFR4 axis targeted therapy may significantly impact liver regeneration after PH.

« Back to 2013 American Transplant Congress