The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Interaction of the Hereditary Hemochromatosis Protein HFE with Transferrin Receptor 2 Is Required for Transferrin-Induced Hepcidin Expression
Open accessAbstract
The mechanisms that allow the body to sense iron levels in order to maintain iron homeostasis are unknown. Patients with the most common form of hereditary iron overload have mutations in the hereditary hemochromatosis protein HFE. They have lower levels of hepcidin than unaffected individuals. Hepcidin, a hepatic peptide hormone, negatively regulates iron efflux from the intestines into the blood. We report two hepatic cell lines, WIF-B cells and HepG2 cells transfected with HFE, where hepcidin expression responded to iron-loaded transferrin. The response was abolished when endogenous transferrin receptor 2 (TfR2) was suppressed or in primary hepatocytes lacking either functional TfR2 or HFE. Furthermore, transferrin-treated HepG2 cells transfected with HFE chimeras containing only the alpha3 and cytoplasmic domains could upregulate hepcidin expression. Since the HFE alpha3 domain interacts with TfR2, these results supported our finding that TfR2/HFE complex is required for transcriptional regulation of hepcidin by holo-Tf.
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“Activation of signaling through the hemochromatosis protein HFE, TFR1, TFR2, or hemojuvelin (HJV), which acts as a co-receptor for bone morphogenetic protein 6 (BMP6), increases hepcidin transcription in a SMAD-dependent fashion.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [198]
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Metadata
- Authors
- Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A.-S., & Enns, C. A.
- Affiliations
- Oregon Health & Science University (US)
- University of Southern California (US)
- Corresponding author
- Enns, Caroline A.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 9
- Issue
- 3
- Pages
- 217-227
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2673483
- OpenAlex
- W2079904892
- Cited by
- 326
- References
- 57
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 10 · 2023: 6 · 2022: 13 · 2021: 19 · 2020: 16 · 2019: 14 · 2018: 12 · 2017: 11 · 2016: 11 · 2015: 19 · 2014: 19 · 2013: 30 · 2012: 22
- FWCI
- 27.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (AA011999, DK072166)
- National Institute on Alcohol Abuse and Alcoholism (P50AA011999)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK054488, R01DK072166, R01DK054488)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hereditary hemochromatosis, HFE gene, transferrin receptor 2, hepcidin, iron homeostasis, iron overload, transferrin, transcriptional regulation, hepatocytes, iron sensing
- MeSH terms
- Hemochromatosis Protein, Animals, Cells, Cultured, Homeostasis, Humans, Iron, Liver, Membrane Proteins, Promoter Regions, Genetic, Receptors, Transferrin, Recombinant Fusion Proteins, Transferrin, Histocompatibility Antigens Class I, Antigens, CD, Mice, Knockout, Hepatocytes, Antimicrobial Cationic Peptides, RNA, Small Interfering, Mice, Hepcidins
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