Revealing the man behind the iron mask – human hepatic iron metabolism gene expression profiles in disorders of iron homeostasis

Aims: Knockout murine models and cellular iron regulatory networks represent a surrogate marker for the human model of iron metabolism. In this study, human hepatic hepcidin (HAMP), hemojuvelin (HJV), transferrin receptor 2 (TfR2), HFE, IL6 and ferroportin mRNA expression patterns are analysed in physiological iron overload, hereditary haemochromatosis (HH) and normal controls.

Methods: Using TaqMan™ qRT PCR, respective gene mRNA expression levels were reported in 43 individuals using the ÄÄCt method of relative quantitation.

Results: HAMP, HJV and ferroportin expression were significantly upregulated in a coordinated fashion in physiological iron overload. Ferroportin was significantly increased in HH (p=0.001). In contrast, hepatic iron overload failed to induce a significant increase in HAMP or HJV expression but significantly reduced TfR2 in HH (p=0.031). A positive correlation existed between ferroportin expression and TS% in HH, suggesting an association between ferroportin levels and circulating transferrin (r=0.708, p=0.01). There was no relationship between HAMP expression and SF, TS% or hepatocellular iron staining. HFE and IL6 expression were not modulated by variations in iron status.

Conclusions: HH subjects have an inappropriate hepatic iron sensing mechanism. TfR2 mRNA expression is decreased with a failure to appropriately upregulate hepcidin and haemojuvelin. However, an appropriate upregulation of ferroportin expression is present.