ArticleProceedings of the National Academy of Sciences of the United States of America2000
Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
- Identification of a common variant in the TFR2 gene implicated in the physiological regulation of serum iron levels.Human molecular genetics · 2011Pooled it
- Assessment of Trace Elements and their Health Impacts from Vegetable Consumption in the Vicinity of the Lolodorf Uranium Deposit, Southern Cameroon.Biological trace element research · 2026Article
- Transferrin Promotes Oligodendroglial Differentiation Independently of Iron Binding and Release.ASN neuro · 2026Article
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Transferrin Receptor 2 in Canine Testicular Tumors: An Emerging Key Role in Seminomas.Animals : an open access journal from MDPI · 2025Article
- EZH2 suppresses ferroptosis in hepatocellular carcinoma and reduces sorafenib sensitivity through epigenetic regulation of TFR2.Cancer science · 2024Article
- Genetics of liver disease in adults.Hepatology communications · 2024Review
- Hepcidin Exacerbates Iron Metabolism Imbalance in Septic Mice.Infection and drug resistance · 2024Article
- Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis-Mechanistic Insights into Anemia of Inflammation and Its Treatment.Nutrients · 2021Review
- Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.The Journal of biological chemistry · 2020Article
- Iron in Neurodegeneration - Cause or Consequence?Frontiers in neuroscience · 2019Review
- Haemochromatosis.Nature reviews. Disease primers · 2018Review
- Iron homeostasis: An anthropocentric perspective.The Journal of biological chemistry · 2017Review
- Mice lacking liver-specific β-catenin develop steatohepatitis and fibrosis after iron overload.Journal of hepatology · 2017Article
- Altered Erythropoiesis in Mouse Models of Type 3 Hemochromatosis.BioMed research international · 2017Article
- PACE4 (PCSK6): another proprotein convertase link to iron homeostasis?Haematologica · 2015Article
- Protein-functionalized PLGA nanoparticles of lamotrigine for neuropathic pain management.AAPS PharmSciTech · 2015Article
- Regulation of cell surface transferrin receptor-2 by iron-dependent cleavage and release of a soluble form.Haematologica · 2015Article
6 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite down-regulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the iron-responsive elements found in the 3' untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE -/-). Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low. In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not down-regulated with dietary iron loading or in the HFE -/- model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.
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