Expression of ferroportin in hemochromatosis liver

Abstract

Iron-regulated transporter protein 1 (IREG1 or ferroportin 1) is a transmembrane iron transporter that has been described in macrophages and hepatocytes. Ferroportin mutations have been described to result in hepatic iron overload in human pedigrees. The role of hepatic ferroportin in the pathogenesis of C282Y-linked hemochromatosis has not been clearly established. The objective was to study the expression of ferroportin mRNA and protein in C282Y-linked hemochromatosis liver and in controls. Human liver biopsies were stained with an anti-ferroportin antibody and quantitation of ferroportin at 62 kDa was done by Western blotting. mRNA was studied by real time RT-PCR. Ferroportin protein expression was increased in C282Y homozygotes (n = 23) compared to wild-type patients (n = 37) (P < 0.003). There was no significant correlation between ferroportin protein or mRNA expression (n = 25) and liver iron concentration or serum ferritin. Immunohistochemical staining demonstrated ferroportin in hepatocytes and macrophages. In conclusion, ferroportin protein is increased in iron-loaded hemochromatosis liver. The increase in ferroportin protein without an increase in mRNA is consistent with iron-mediated translational regulation through the 5'IRE in the mRNA.