Erratum to: HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication

Background: In liver hepatocytes, the HFE gene regulates cellular and systemic iron homeostasis by modulating cellular iron-uptake and producing the iron-hormone hepcidin in response to systemic iron elevation. However, the mechanism of iron-sensing in hepatocytes remain enigmatic. Therefore, to study the effect of iron on HFE and hepcidin (HAMP) expressions under distinct extracellular and intracellular iron-loading, we examined the effect of holotransferrin treatment (1,2, 5 and 8 g/L for 6 h) on intracellular iron levels, and mRNA expressions of HFE and HAMP in wild-type HepG2 and previously characterized iron-loaded recombinant-TfR1 HepG2 cells.

Methods and Results: Gene expression was analyzed by real-time PCR and intracellular iron was measured by ferrozine assay. Data showed that in the wild-type cells, where intracellular iron content remained unchanged, HFE expression remained unaltered at low holotransferrin treatments but was upregulated upon 5 g/L (p<0.04) and 8 g/L (p=0.05) treatments. HAMP expression showed alternating elevations and increased upon 1 g/L (p<0.05) and 5 g/L (p<0.05). However, in the recombinant cells that showed higher intracellular iron levels than wild-type cells, HFE and HAMP expressions were elevated only at low 1 g/L treatment (p<0.03) and were repressed at 2 g/L (p<0.03) treatment. Under holotransferrin-untreated conditions, the iron-loaded recombinant cells showed higher expressions of HFE (p<0.03) and HAMP (p=0.05) than wild-type cells.

Conclusions: HFE mRNA was independently elevated by extracellular and intracellular iron-excess. Thus, it may be involved in sensing both, extracellular and intracellular iron. Repression of HAMP expression under simultaneous intracellular and extracellular iron-loading resembles certain iron-excess pathologies.

This is a pre-print of an article published in Molecular Biology Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11033-017-4127-y