Hepcidin plays a negative role in liver regeneration.

Hepcidin is a key regulator of iron metabolism. The expression of hepcidin is significantly induced by iron overload, inflammation, and infection of pathogens. Recent studies have indicated that the expression of hepcidin in the liver is also regulated during liver regeneration. However, the mechanism of the regulation of hepcidin expression and its role in liver regeneration remain unclear. In this study, we found that the hepatocyte growth factor inhibited hepcidin expression in the liver during the late stage of liver regeneration. Meanwhile, we investigated the effect of hepcidin on liver regeneration. Mice overexpressing hepcidin-1 exhibited impaired hepatic regeneration after partial hepatectomy, as determined by immunohistochemical staining of the proliferation cell nuclear antigen. Our results demonstrated a negative role of hepcidin in modulating liver regeneration, and suggested that a sustained high iron level by the down-regulation of hepcidin at the late stage of liver regeneration is required for hepatocyte proliferation.