Downregulation of hepcidin and haemojuvelin expression in the hepatocyte cell-line HepG2 induced by thalassaemic sera

Br J Haematol. 2006 Oct;135(1):129-38. doi: 10.1111/j.1365-2141.2006.06258.x. Epub 2006 Aug 25.


Beta-thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of beta-thalassaemia, we observed that the liver expressed relatively low levels of hepcidin, which is a key factor in the regulation of iron absorption by the gut and of iron recycling by the reticuloendothelial system. It was hypothesised that, despite the overt iron overload, a putative plasma factor found in beta-thalassaemia might suppress liver hepcidin expression. Sera from beta-thalassaemia and haemochromatosis (C282Y mutation) patients were compared with those of healthy individuals regarding their capacity to induce changes the expression of key genes of iron metabolism in human HepG2 hepatoma cells. Sera from beta-thalassaemia major patients induced a major decrease in hepcidin (HAMP) and lipocalin2 (oncogene 24p3) (LCN2) expression, as well as a moderate decrease in haemojuvelin (HFE2) expression, compared with sera from healthy individuals. A significant correlation was found between the degree of downregulation of HAMP and HFE2 induced by beta-thalassaemia major sera (r = 0.852, P < 0.0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from beta-thalassaemia intermedia patients. In contrast, the majority of sera from hereditary haemochromatosis patients induced an increase in HAMP expression, which correlated with transferrin (Tf) saturation (r = 0.765, P < 0.0099). Our results suggest that, in beta-thalassaemia, serum factors might override the potential effect of iron overload on HAMP expression, thereby providing an explanation for the failure to arrest excessive intestinal iron absorption in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Antimicrobial Cationic Peptides / biosynthesis*
  • Antimicrobial Cationic Peptides / genetics
  • Blood Transfusion
  • Cell Line
  • Down-Regulation*
  • GPI-Linked Proteins
  • Hemochromatosis / blood
  • Hemochromatosis Protein
  • Hepatocytes / metabolism*
  • Hepcidins
  • Humans
  • Lipocalin-2
  • Lipocalins
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Polymerase Chain Reaction / methods
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • beta-Thalassemia / blood*
  • beta-Thalassemia / therapy


  • Acute-Phase Proteins
  • Antimicrobial Cationic Peptides
  • GPI-Linked Proteins
  • HAMP protein, human
  • HJV protein, human
  • Hamp protein, mouse
  • Hemochromatosis Protein
  • Hepcidins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Membrane Proteins
  • Proto-Oncogene Proteins