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

Kosha J. Mehta, Sebastien Farnaud, Vinood B. Patel

    Research output: Contribution to journalArticlepeer-review

    3 Citations (Scopus)
    45 Downloads (Pure)

    Abstract

    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. 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 treatment (p < 0.03). 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. 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 non-hereditary iron-excess pathologies.

    Original languageEnglish
    Pages (from-to)399-403
    Number of pages5
    JournalMolecular Biology Reports
    Volume44
    Issue number5
    Early online date24 Aug 2017
    DOIs
    Publication statusPublished - 19 Sept 2017

    Keywords

    • Hepcidin
    • HFE
    • Holotransferrin
    • Iron-sensing

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics

    Fingerprint

    Dive into the research topics of 'HFE mRNA expression is responsive to intracellular and extracellular iron loading: short communication'. Together they form a unique fingerprint.

    Cite this