Hepcidin expression in vivo is regulated in proportion to iron status (i.e. increased by iron loading and decreased in iron deficiency). However, in vitro studies with hepatoma cell lines often show an inverse relationship between iron status and hepcidin expression. Here, we investigated possible molecular mechanisms responsible for the differences in iron sensing between hepatoma cell lines and human primary hepatocytes. RNA was collected from primary human hepatocytes, and HepG2 and HuH7 hepatoma cells treated with either transferrin-bound- and non-transferrin-bound-iron. Expression of hepcidin, transferrin receptor 2, HFE and hemojuvelin were quantified using real-time PCR. Hepcidin expression was increased in primary human hepatocytes following 24 hour exposure to holo-ferric transferrin. In contrast hepcidin mRNA levels in hepatoma cells were decreased by transferrin. Hepcidin expression was positively correlated with transferrin receptor 2 mRNA levels in primary human hepatocytes. Compared with primary hepatocytes, transferrin receptor 2 expression was significantly lower in hepatoma cell lines; furthermore, there was no correlation between transferrin receptor 2 and hepcidin mRNA levels in either HepG2 or HuH7 cells. Taken together our data suggest that transferrin receptor 2 is a likely candidate to explain the differences in iron sensing between hepatoma cell lines and primary human hepatocytes.
- Copyright © 2010, American Journal of Physiology- Gastrointestinal and Liver Physiology