mRNA expression of iron regulatory genes in β-thalassemia intermedia and β-thalassemia major mouse models

Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rachmilewitz, Eliezer; Breda, Laura; Rivella, Stefano; Rechavi, Gideon

doi:10.1002/ajh.20549

Cited by 71Iron Metabolism and DisordersHemoglobinopathies and Related DisordersHemoglobin structure and function

mRNA expression of iron regulatory genes in β-thalassemia intermedia and β-thalassemia major mouse models

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Weizer-Stern, Orly, Adamsky, Konstantin, Amariglio, Ninette, Rachmilewitz, Eliezer, Breda, Laura, Rivella, Stefano, Rechavi, Gideon·2006·American Journal of Hematology

DOI 10.1002/ajh.20549

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Abstract

beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-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 result 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 beta-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 beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

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The hypoxic response (decreased hepcidin) seems to dominate that due to inflammation (increased hepcidin) even when iron levels are high.
“with in many cases the hypoxic response (decreased hepcidin) seeming to dominate that due to inflammation (increased hepcidin) even when iron levels are high [352,353].”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [352]
Thalassaemia predisposes towards PE and causes hepcidin to decrease and NGAL to increase, with consequent iron dysregulation.
“We note in this context that thalassaemia not only predisposes towards PE but is known in general to cause hepcidin to decrease and NGAL to increase [352,353,356,535], with consequent and inevitable iron dysregulation.”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [352]

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Decreased hepcidin mRNA expression in thalassemic mice
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Authors: Weizer-Stern, O., Adamsky, K., Amariglio, N., Rachmilewitz, E., Breda, L., Rivella, S., & Rechavi, G.
Affiliations: Tel Aviv University (IL)
Wolfson Medical Center (IL)
Cornell University (US)
Corresponding author: Rechavi, Gideon
ORCID: Amariglio, Ninette
Breda, Laura
Rivella, Stefano
Rechavi, Gideon
Venue: American Journal of Hematology
Publisher: Wiley
Published: 2006
Volume: 81
Issue: 7
Pages: 479-483
ISSN: 0361-8609 (ISSN-L)
1096-8652
DOI: 10.1002/ajh.20549
OpenAlex: W2011735860
Cited by: 71
References: 32
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 2 · 2012: 4
FWCI: 4.86
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 3530 d)
Locations: American Journal of Hematology (publishedVersion)
PubMed (publishedVersion)
Funders: Cooley's Anemia Foundation
Hebrew University of Jerusalem
Sackler Faculty of Medicine, Tel-Aviv University
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords: beta-thalassemia major, beta-thalassemia intermedia, hepcidin, iron regulatory genes, iron overload, iron absorption, transferrin receptor 1, transferrin receptor 2, neutrophil gelatinase-associated lipocalin, ineffective erythropoiesis, mouse model, hepatic gene expression
MeSH terms: Lipocalin-2, Acute-Phase Proteins, Animals, Disease Models, Animal, Erythropoiesis, Female, Genes, Regulator, Globins, Humans, Intestinal Absorption, Iron, Receptors, Transferrin, Oncogene Proteins, Down-Regulation, Erythroid Precursor Cells, beta-Thalassemia, Iron Overload, Gene Expression Profiling, Antimicrobial Cationic Peptides, Mice, Lipocalins, Hepcidins

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mRNA expression of iron regulatory genes in β-thalassemia intermedia and β-thalassemia major mouse models

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