ArticleBlood2010
Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 76 citations in OpenAlex.
- Mechanism and regulation of iron absorption throughout the life cycle.Journal of advanced research · 2025Review
- Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.Blood advances · 2024Article
- In vivo adenine base editing reverts C282Y and improves iron metabolism in hemochromatosis mice.Nature communications · 2022Article
- Ferroptosis and Its Emerging Role in Pre-Eclampsia.Antioxidants (Basel, Switzerland) · 2022Review
- Evaluation of the Association of Transferrin Receptor Type 2 Gene Mutation (Y250X) with Iron Overload in Major β- Thalassemia.Archives of Razi Institute · 2021Article
- Restriction of Manganese Intake Prevents the Onset of Brain Manganese Overload inInternational journal of molecular sciences · 2021Article
- Article
- Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains.Physiological reports · 2020Article
- Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.The Journal of biological chemistry · 2020Article
- Hepatic heparan sulfate is a master regulator of hepcidin expression and iron homeostasis in human hepatocytes and mice.The Journal of biological chemistry · 2019Article
- The catalytic, stem, and transmembrane portions of matriptase-2 are required for suppressing the expression of the iron-regulatory hormone hepcidin.The Journal of biological chemistry · 2019Article
- What can we learn from ineffective erythropoiesis in thalassemia?Blood reviews · 2018Review
- The hemochromatosis protein HFE signals predominantly via the BMP type I receptor ALK3 in vivo.Communications biology · 2018Article
- Ultrafiltered recombinant AAV8 vector can be safely administered in vivo and efficiently transduces liver.PloS one · 2018Article
- Relationship between Hepatitis C Virus Infection and Iron Overload.Chinese medical journal · 2017Review
- Effect of erythropoietin administration on proteins participating in iron homeostasis in Tmprss6-mutated mask mice.PloS one · 2017Article
- New strategies to target iron metabolism for the treatment of beta thalassemia.Annals of the New York Academy of Sciences · 2016Review
- Heparanase Overexpression Reduces Hepcidin Expression, Affects Iron Homeostasis and Alters the Response to Inflammation.PloS one · 2016Article
- Effects of developmental iron deficiency and post-weaning iron repletion on the levels of iron transporter proteins in rats.Nutrition research and practice · 2015Article
- CD81 promotes both the degradation of transferrin receptor 2 (TfR2) and the Tfr2-mediated maintenance of hepcidin expression.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Hereditary hemochromatosis is caused by mutations in the hereditary hemochromatosis protein (HFE), transferrin-receptor 2 (TfR2), hemojuvelin, hepcidin, or ferroportin genes. Hepcidin is a key iron regulator, which is secreted by the liver, and decreases serum iron levels by causing the down-regulation of the iron transporter, ferroportin. Mutations in either HFE or TfR2 lower hepcidin levels, implying that both HFE and TfR2 are necessary for regulation of hepcidin expression. In this study, we used a recombinant adeno-associated virus, AAV2/8, for hepatocyte-specific expression of either Hfe or Tfr2 in mice. Expression of Hfe in Hfe-null mice both increased Hfe and hepcidin mRNA and lowered hepatic iron and Tf saturation. Expression of Tfr2 in Tfr2-deficient mice had a similar effect, whereas expression of Hfe in Tfr2-deficient mice or of Tfr2 in Hfe-null mice had no effect on liver or serum iron levels. Expression of Hfe in wild-type mice increased hepcidin mRNA and lowered iron levels. In contrast, expression of Tfr2 had no effect on wild-type mice. These findings suggest that Hfe is limiting in formation of the Hfe/Tfr2 complex that regulates hepcidin expression. In addition, these studies show that the use of recombinant AAV vector to deliver genes is a promising approach for studying physiologic consequences of protein complexes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.