ArticleBlood2023
Regulation of iron homeostasis by hepatocyte TfR1 requires HFE and contributes to hepcidin suppression in β-thalassemia.
Article in Blood, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 36 citations in OpenAlex.
- The neogenin-hemojuvelin axis in murine liver is crucial for hepcidin expression.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- The convergent roles of metabolic dysfunction, alcohol, and iron in steatotic liver disease: a review.Bioscience reports · 2026Review
- Disruption of cellular iron homeostasis by SRPX2-IRP1 interaction aggravates renal fibrosis in chronic kidney disease.Cell death and differentiation · 2026Article
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.Biomolecules · 2026Review
- NOX1/4 drives hepatic iron and lipid dysregulation, redox imbalance, and inflammation in ethanol-fed mice.Scientific reports · 2026Article
- Ferrostatin 1 exerts multifaceted hepatic protection against alcoholic liver injury by inhibiting ferroptosis.Scientific reports · 2026Article
- Current research on the HIF-2α-EPO-Hb axis in hypoxic environments: from molecular mechanisms to clinical.Frontiers in medicine · 2026Review
- Iron Overload Mediates the Differential Cell Fate of Astrocytes from Neurons and Its Regulatory Mechanisms in Ischemic Stroke.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics.Current molecular medicine · 2026Review
- Adipocytes orchestrate obesity-related chronic inflammation through β2-microglobulin.Signal transduction and targeted therapy · 2025Article
- Immune cells dying from ferroptosis: mechanisms and therapeutic opportunities.Cell death & disease · 2025Review
- Ferroptosis-mediated osteoclast-osteoblast crosstalk: signaling pathways governing bone remodeling in osteoporosis.Journal of orthopaedic surgery and research · 2025Review
- Exploring the role of ferroptosis in esophageal cancer: mechanisms and therapeutic implications.Cell death discovery · 2025Review
- HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease.Biomedicines · 2025Review
- Article
- Outline of Iron Metabolism, with Emphasis on Erythroid Cells.Mediterranean journal of hematology and infectious diseases · 2025Review
- Global Proteomics Indicates Subcellular-Specific Anti-Ferroptotic Responses to Ionizing Radiation.Molecular & cellular proteomics : MCP · 2025Article
- Cardiac injury caused by iron overload in thalassemia.Frontiers in pediatrics · 2025Review
- Exploratory Study on the Role of Emodin in Alleviating MPTP-Induced Neurotoxicity: A Focus on p53-Ferroptosis Signaling.Drug design, development and therapy · 2025Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Transferrin receptor 1 (TfR1) performs a critical role in cellular iron uptake. Hepatocyte TfR1 is also proposed to influence systemic iron homeostasis by interacting with the hemochromatosis protein HFE to regulate hepcidin production. Here, we generated hepatocyte Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), either alone or together with Hfe knockout or β-thalassemia, to investigate the extent to which hepatocyte TfR1 function depends on HFE, whether hepatocyte TfR1 impacts hepcidin regulation by serum iron and erythropoietic signals, and its contribution to hepcidin suppression and iron overload in β-thalassemia. Compared with Tfrcfl/fl;Alb-Cre- controls, Tfrcfl/fl;Alb-Cre+ mice displayed reduced serum and liver iron; mildly reduced hematocrit, mean cell hemoglobin, and mean cell volume; increased erythropoietin and erythroferrone; and unchanged hepcidin levels that were inappropriately high relative to serum iron, liver iron, and erythroferrone levels. However, ablation of hepatocyte Tfrc had no impact on iron phenotype in Hfe knockout mice. Tfrcfl/fl;Alb-Cre+ mice also displayed a greater induction of hepcidin by serum iron compared with Tfrcfl/fl;Alb-Cre- controls. Finally, although acute erythropoietin injection similarly reduced hepcidin in Tfrcfl/fl;Alb-Cre+ and Tfrcfl/fl;Alb-Cre- mice, ablation of hepatocyte Tfrc in a mouse model of β-thalassemia intermedia ameliorated hepcidin deficiency and liver iron loading. Together, our data suggest that the major nonredundant function of hepatocyte TfR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine β-thalassemia.
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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.