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

Orly Weizer-Stern, Konstantin Adamsky, Ninette Amariglio, Carina Levin, Ariel Koren, William Breuer, Eliezer Rachmilewitz, Laura Breda, Stefano Rivella, Z. Ioav Cabantchik, Gideon Rechavi

Research output: Contribution to journalArticlepeer-review

Abstract

β-Thalassaemia represents a group of diseases, in which ineffective erythropoiesis is accompanied by iron overload. In a mouse model of β-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 β-thalassaemia might suppress liver hepcidin expression. Sera from β-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 β-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 β-thalassaemia major sera (r = 0.852, P < 0.0009). Decreased HAMP expression was also found in HepG2 cells treated with sera from β-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 β-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.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalBritish Journal of Haematology
Volume135
Issue number1
DOIs
StatePublished - Oct 2006

Keywords

  • Haemochromatosis
  • Haemojuvelin
  • Hepcidin
  • Iron
  • Thalassaemia

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