TY - JOUR
T1 - mRNA expression of iron regulatory genes in β-thalassemia intermedia and β-thalassemia major mouse models
AU - Weizer-Stern, Orly
AU - Adamsky, Konstantin
AU - Amariglio, Ninette
AU - Rachmilewitz, Eliezer
AU - Breda, Laura
AU - Rivella, Stefano
AU - Rechavi, Gideon
PY - 2006/7
Y1 - 2006/7
N2 - β-Thalassemia is an inherited anemia in which synthesis of the hemoglobin β-chain is decreased. The excess unmatched α-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of β-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and resuit in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of β-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in β-thalassemia major mouse model (C57BI/6 Hbbth3/th3), and compared it with β-thalassemia intermedia mouse model (C57BI/6 Hbb th3/th3) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the β-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in β-thalassemia major, despite Iron overload, might explain the increased iron absorption typically observed in thalassemia.
AB - β-Thalassemia is an inherited anemia in which synthesis of the hemoglobin β-chain is decreased. The excess unmatched α-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of β-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and resuit in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of β-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in β-thalassemia major mouse model (C57BI/6 Hbbth3/th3), and compared it with β-thalassemia intermedia mouse model (C57BI/6 Hbb th3/th3) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the β-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in β-thalassemia major, despite Iron overload, might explain the increased iron absorption typically observed in thalassemia.
KW - HFE
KW - Hepcidin
KW - IREG
KW - Iron absorption
KW - Murine
KW - NGAL
KW - Transferrin receptor
KW - β-thalassemia
UR - http://www.scopus.com/inward/record.url?scp=33745684771&partnerID=8YFLogxK
U2 - 10.1002/ajh.20549
DO - 10.1002/ajh.20549
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C2 - 16755567
AN - SCOPUS:33745684771
SN - 0361-8609
VL - 81
SP - 479
EP - 483
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 7
ER -