ArticleHaematologica2014
The erythroid function of transferrin receptor 2 revealed by Tmprss6 inactivation in different models of transferrin receptor 2 knockout mice.
Article in Haematologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Genomic Signatures Underlying Environmental Adaptation and Reproductive Traits in the Tibetan Pig.Animals : an open access journal from MDPI · 2026Article
- The role of redox-active iron, copper, manganese, and redox-inactive zinc in toxicity, oxidative stress, and human diseases.EXCLI journal · 2025Review
- Coexistence of Multiple Gene Variants in Some Patients with Erythrocytoses.Mediterranean journal of hematology and infectious diseases · 2024Article
- Heme-deficient primitive red blood cells induce HSPC ferroptosis by altering iron homeostasis during zebrafish embryogenesis.Development (Cambridge, England) · 2023Article
- Transferrin Receptors in Erythropoiesis.International journal of molecular sciences · 2020Review
- Correcting β-thalassemia by combined therapies that restrict iron and modulate erythropoietin activity.Blood · 2020Article
- Marathon Run-induced Changes in the Erythropoietin-Erythroferrone-Hepcidin Axis are Iron Dependent.International journal of environmental research and public health · 2020Article
- Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.The Journal of biological chemistry · 2020Article
- Lobe specificity of iron binding to transferrin modulates murine erythropoiesis and iron homeostasis.Blood · 2019Article
- Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling.Nature metabolism · 2019Article
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- The Functional Versatility of Transferrin Receptor 2 and Its Therapeutic Value.Pharmaceuticals (Basel, Switzerland) · 2018Review
- What can we learn from ineffective erythropoiesis in thalassemia?Blood reviews · 2018Review
- The relationship between systemic iron homeostasis and erythropoiesis.Bioscience reports · 2017Review
- Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis.BioMed research international · 2017Article
- The Regulation of Iron Absorption and Homeostasis.The Clinical biochemist. Reviews · 2016Review
- Is erythroferrone finally the long sought-after systemic erythroid regulator of iron?World journal of biological chemistry · 2015Article
- Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form.Haematologica · 2015Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Transferrin receptor 2 (TFR2) is a transmembrane glycoprotein expressed in the liver and in the erythroid compartment, mutated in a form of hereditary hemochromatosis. Hepatic TFR2, together with HFE, activates the transcription of the iron-regulator hepcidin, while erythroid TFR2 is a member of the erythropoietin receptor complex. The TMPRSS6 gene, encoding the liver-expressed serine protease matriptase-2, is the main inhibitor of hepcidin and inactivation of TMPRSS6 leads to iron deficiency with high hepcidin levels. Here we evaluate the phenotype resulting from the genetic loss of Tmprss6 in Tfr2 total (Tfr2(-/-)) and liver-specific (Tfr2(LCKO)) knockout mice. Tmprss6(-/-)Tfr2(-/-) and Tmprss6(-/-)Tfr2(LCKO) mice have increased hepcidin levels and show iron-deficiency anemia like Tmprss6(-/-)mice. However, while Tmprss6(-/-)Tfr2(LCKO) are phenotypically identical to Tmprss6(-/-) mice, Tmprss6(-/-)Tfr2(-/-) mice have increased red blood cell count and more severe microcytosis than Tmprss6(-/-) mice. In addition hepcidin expression in Tmprss6(-/-)Tfr2(-/-) mice is higher than in the wild-type animals, but lower than in Tmprss6(-/-) mice, suggesting partial inhibition of the hepcidin activating pathway. Our results prove that hepatic TFR2 acts upstream of TMPRSS6. In addition Tfr2 deletion causes a relative erythrocytosis in iron-deficient mice, which likely attenuates the effect of over-expression of hepcidin in Tmprss6(-/-) mice. Since liver-specific deletion of Tfr2 in Tmprss6(-/-) mice does not modify the erythrocyte count, we speculate that loss of Tfr2 in the erythroid compartment accounts for the hematologic phenotype of Tmprss6(-/-)Tfr2(-/-) mice. We propose that TFR2 is a limiting factor for erythropoiesis, particularly in conditions of iron restriction.
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