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Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia
  1. H Kulaksiz1,
  2. S G Gehrke1,
  3. A Janetzko2,
  4. D Rost1,
  5. T Bruckner3,
  6. B Kallinowski1,
  7. W Stremmel1
  1. 1Department of Internal Medicine, Division of Gastroenterology, University Hospital Heidelberg, Heidelberg, Germany
  2. 2DRG Instruments GmbH, Marburg, Germany
  3. 3Department of Social Medicine, Occupational and Environmental Dermatology, University Hospital Heidelberg, Heidelberg, Germany
  1. Correspondence to:
    Dr H Kulaksiz
    Department of Internal Medicine, Division of Gastroenterology, Bergheimer Str 58, D-69115 Heidelberg, Germany; Hasan_Kulaksizmed.uni-heidelberg.de

Abstract

Background and aims: The hepatic peptide hormone hepcidin, which has recently been isolated from human plasma and urine, is thought to be a central regulator of iron homeostasis. We investigated the presence and cellular localisation of hepcidin in the liver and developed a non-invasive assay to analyse its regulation in patients with hereditary haemochromatosis (HH), chronic renal insufficiency (CRI), and renal anaemia (RA).

Methods: Expression and localisation of hepcidin was shown by reverse transcription-polymerase chain reaction, western blot, immunocytochemistry, and immunofluorescence in human and guinea pig liver. Serum concentrations were determined in various groups of patients using a sensitive enzyme linked immunosorbent assay (ELISA).

Results: Western blot analysis with region specific antibodies identified a ~10 kDa peptide corresponding to the apparent molecular mass of pro-hepcidin. Localisation studies revealed that pro-hepcidin is expressed at the basolateral membrane domain of hepatocytes and is also present in blood. We developed a stable sensitive ELISA for detection and determination of pro-hepcidin in human serum. Mean pro-hepcidin level in human serum of healthy volunteers was 106.2 ng/ml. Enhanced levels of pro-hepcidin (148.1 ng/ml) were found in patients with CRI but normal haemoglobin values, indicating that the kidneys may metabolise and/or eliminate the circulating hormone. In contrast, concentrations of pro-hepcidin were significantly decreased in patients with HH (70.2 ng/ml) and also in patients with RA (115.0 ng/ml) compared with the CRI group.

Conclusions: From the detection of pro-hepcidin in human serum, we conclude that the prohormone may be involved in the regulation of iron metabolism in HH. Decreased pro-hepcidin levels could play an important role in the pathogenesis of HH.

  • hepcidin
  • chronic renal insufficiency
  • iron absorption
  • hereditary haemochromatosis
  • liver
  • aa, amino acid
  • CRI, chronic renal insufficiency
  • ELISA, enzyme linked immunosorbent assay
  • EPO, erythropoietin
  • HH, hereditary haemochromatosis
  • PBS, phosphate buffered saline
  • RA, renal anaemia
  • RT-PCR, reverse transcription-polymerase chain reaction
  • TfR1, classical transferrin receptor
  • TfR2, transferrin receptor type 2
  • TBS, Tris buffered saline

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