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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of signaling through HFE, TFR1, TFR2, or HJV increases hepcidin transcription in a SMAD-dependent fashion.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization
Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., & Kaplan, J. (2004) · Science · doi:10.1126/science.1104742 · Cited by 4,803 · see citing works
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-399 · Cited by 3,664 · see citing works
Firefly Luciferase Gene: Structure and Expression in Mammalian Cells
de Wet, J. R., Wood, K. V., DeLuca, M., Helinski, D. R., & Subramani, S. E. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.2.725 · Cited by 3,088 · see citing works
Pigeon, C., Ilyin, G., Courselaud, B., Leroyer, P., Turlin, B., Brissot, P., & Loréal, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008923200 · Cited by 1,697 · see citing works
Mutations in HFE2 cause iron overload in chromosome 1q–linked juvenile hemochromatosis
Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L. E., Franchini, P. L., Dubé, M.-P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., et al. (2004) · Nature Genetics · doi:10.1038/ng1274 · Cited by 974 · see citing works
Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis
Roetto, A., Papanikolaou, G., Politou, M., Alberti, F., Girelli, D., Christakis, J., Loukopoulos, D., & Camaschella, C. (2003) · Nature Genetics · doi:10.1038/ng1053 · Cited by 860 · see citing works
Feder, J. N., Penny, D. M., Irrinki, A., Lee, V. K., Lebrón, J. A., Watson, N., Tsuchihashi, Z., Sigal, E., Bjorkman, P. J., & Schatzman, R. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1472 · Cited by 827 · see citing works
The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22
Camaschella, C., Roetto, A., Calì, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., & Gasparini, P. (2000) · Nature Genetics · doi:10.1038/75534 · Cited by 803 · see citing works
Molecular Cloning of Transferrin Receptor 2
Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gombart, A. F., & Koeffler, H. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20826 · Cited by 646 · see citing works
Lebrón, J., Bennett, M. J., Vaughn, D., Chirino, A., Snow, P., Mintier, G., Feder, J., & Bjorkman, P. (1998) · Cell · doi:10.1016/s0092-8674(00)81151-4 · Cited by 636 · see citing works
Weinstein, D. A., Roy, C. N., Fleming, M. D., Loda, M. F., Wolfsdorf, J. I., & Andrews, N. C. (2002) · Blood · doi:10.1182/blood-2002-04-1260 · Cited by 632 · see citing works
Bridle, K. R., Frazer, D. M., Wilkins, S. J., Dixon, J. L., Purdie, D. M., Crawford, D. H., Subramaniam, V. N., Powell, L. W., Anderson, G. J., & Ramm, G. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12602-5 · Cited by 620 · see citing works
Autosomal-dominant hemochrom-atosis is associated with a mutation in the ferroportin (SLC11A3) gene
Montosi, G., Donovan, A., Totaro, A., Garuti, C., Pignatti, E., Cassanelli, S., Trenor, C. C., Gasparini, P., Andrews, N. C., & Pietrangelo, A. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13468 · Cited by 555 · see citing works
HFE gene knockout produces mouse model of hereditary hemochromatosis
Zhou, X. Y., Tomatsu, S., Fleming, R. E., Parkkila, S., Waheed, A., Jiang, J., Fei, Y., Brunt, E. M., Ruddy, D. A., Prass, C. E., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2492 · Cited by 519 · see citing works
Feder, J. N., Tsuchihashi, Z., Irrinki, A., Lee, V. K., Mapa, F. A., Morikang, E., Prass, C. E., Starnes, S. M., Wolff, R. K., Parkkila, S., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.22.14025 · Cited by 471 · see citing works
Regulation of iron acquisition and storage: consequences for iron-linked disorders
De Domenico, I., McVey Ward, D., & Kaplan, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2295 · Cited by 464 · see citing works
Goswami, T., & Andrews, N. C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c600197200 · Cited by 352 · cited 3× · see citing works
“They speculate that the binding partner was TfR2 based on previous evidence showing that HFE is capable of binding to TfR2 (Chen et al., 2007; Goswami and Andrews, 2006).”
BackgroundThe Transferrin Receptor Modulates Hfe-Dependent Regulation of Hepcidin Expression
Schmidt, P. J., Toran, P. T., Giannetti, A. M., Bjorkman, P. J., & Andrews, N. C. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.016 · Cited by 345 · see citing works
Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor
Bennett, M. J., Lebrón, J. A., & Björkman, P. J. (2000) · Nature · doi:10.1038/47417 · Cited by 338 · see citing works
Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis
Nicolas, G., Viatte, L., Lou, D.-Q., Bennoun, M., Beaumont, C., Kahn, A., Andrews, N. C., & Vaulont, S. (2003) · Nature Genetics · doi:10.1038/ng1150 · Cited by 311 · see citing works
Muckenthaler, M. U., Roy, C. N., Custodio, Á. O., Miñana, B., DEGRAAF, J., Montross, L. K., Andrews, N. C., & Hentze, M. W. (2003) · Nature Genetics · doi:10.1038/ng1152 · Cited by 293 · see citing works
Decreased Liver Hepcidin Expression in the Hfe Knockout Mouse
Ahmad, K. A., Ahmann, J. R., Migas, M. C., Waheed, A., Britton, R. S., Bacon, B. R., Sly, W. S., & Fleming, R. E. (2002) · Blood Cells Molecules and Diseases · doi:10.1006/bcmd.2002.0575 · Cited by 276 · see citing works
Lin, L., Valore, E. V., Nemeth, E., Goodnough, J. B., Gabayan, V., & Ganz, T. (2007) · Blood · doi:10.1182/blood-2007-04-087593 · Cited by 267 · see citing works
The C282Y Mutation Causing Hereditary Hemochromatosis Does Not Produce a Null Allele
Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D., & Andrews, N. C. (1999) · Blood · doi:10.1182/blood.v94.1.9.413a43_9_11 · Cited by 259 · see citing works
Gehrke, S. G., Kulaksiz, H., Herrmann, T. R. W., Riedel, H.-D., Bents, K., Veltkamp, C., & Stremmel, W. (2003) · Blood · doi:10.1182/blood-2002-11-3610 · Cited by 244 · see citing works
Association of HFE protein with transferrin receptor in crypt enterocytes of human duodenum
Waheed, A., Parkkila, S., Saarnio, J., Fleming, R. E., Zhou, X. Y., Tomatsu, S., Britton, R. S., Bacon, B. R., & Sly, W. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.4.1579 · Cited by 243 · see citing works
Kawabata, H., Fleming, R. E., Gui, D., Moon, S. Y., Saitoh, T., O’Kelly, J., Umehara, Y., Wano, Y., SAID, J. W., & Koeffler, H. P. (2004) · Blood · doi:10.1182/blood-2004-04-1416 · Cited by 238 · see citing works
Diferric transferrin regulates transferrin receptor 2 protein stability
Johnson, M. B., & Enns, C. A. (2004) · Blood · doi:10.1182/blood-2004-06-2477 · Cited by 230 · see citing works
Self-citationWIF-B cells: an in vitro model for studies of hepatocyte polarity.
Ihrke, G., Neufeld, E. B., Meads, T., Shanks, M. R., Cassio, D., Laurent, M., Schroer, T. A., Pagano, R. E., & Hubbard, A. L. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.123.6.1761 · Cited by 208 · see citing works
Regulation of transferrin receptor 2 protein levels by transferrin
Robb, A., & Wessling‐Resnick, M. (2004) · Blood · doi:10.1182/blood-2004-06-2481 · Cited by 204 · see citing works
Zhang, A., Xiong, S., Tsukamoto, H., & Enns, C. A. (2003) · Blood · doi:10.1182/blood-2003-07-2378 · Cited by 174 · see citing works
Self-citationHfe Acts in Hepatocytes to Prevent Hemochromatosis
Spasić, M. V., Kiss, J., Herrmann, T. R. W., Galy, B., Martinache, S., Stolte, J., Gröne, H., Stremmel, W., Hentze, M. W., & Muckenthaler, M. U. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.014 · Cited by 150 · see citing works
Verga Falzacappa, M. V., Casanovas, G., Hentze, M. W., & Muckenthaler, M. U. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0313-7 · Cited by 146 · see citing works
Hereditary hemochromatosis: etiologic, pathologic, and clinical aspects.
Bothwell, T. H., & MacPhail, A. P. (1998) · PubMed · Cited by 141 · see citing works
West, A. P., Giannetti, A. M., Herr, A. B., Bennett, M. J., Nangiana, J. S., Pierce, J. R., Weiner, L. P., Snow, P. M., & Björkman, P. J. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5048 · Cited by 125 · see citing works
Targeted Disruption of the Hepatic Transferrin Receptor 2 Gene in Mice Leads to Iron Overload
Wallace, D. F., Summerville, L., & Subramaniam, V. N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.11.028 · Cited by 124 · see citing works
Mechanism for Multiple Ligand Recognition by the Human Transferrin Receptor
Giannetti, A. M., Snow, P. M., Zak, O., & Björkman, P. J. (2003) · PLoS Biology · doi:10.1371/journal.pbio.0000051 · Cited by 122 · see citing works
Evidence That Inhibition of Hemojuvelin Shedding in Response to Iron Is Mediated through Neogenin
Zhang, A., Anderson, S. A., Meyers, K. R., Hernandez, C., Eisenstein, R. S., & Enns, C. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m608788200 · Cited by 117 · see citing works
Self-citationGao, J., Zhao, N., Knutson, M. D., & Enns, C. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803150200 · Cited by 89 · see citing works
Self-citationExpression of the Apical Conjugate Export Pump, Mrp2, in the Polarized Hepatoma Cell Line, Wif–B
Nies, A. T., Cantz, T., Brom, M., Leier, I., & KEPPLER, D. O. R. (1998) · Hepatology · doi:10.1002/hep.510280523 · Cited by 84 · see citing works
Lebrón, J. A., & Björkman, P. J. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.2842 · Cited by 83 · see citing works
Chen, J., Chloupková, M., Gao, J., Arvedson, T., & Enns, C. A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706720200 · Cited by 81 · see citing works
Self-citationFeng, Y., & Longmore, G. D. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.10.4010-4022.2005 · Cited by 81 · see citing works
Dual Luminescence-Based Reporter Gene Assay for Luciferase andβ-Galactosidase
Martin, C., Wight, P. A., Dobretsova, A., & Bronstein, I. (1996) · BioTechniques · doi:10.2144/96213pf01 · Cited by 66 · see citing works
Heterotypic interactions between transferrin receptor and transferrin receptor 2
Vogt, T. M., Blackwell, A. D., Giannetti, A. M., Björkman, P. J., & Enns, C. A. (2003) · Blood · doi:10.1182/blood-2002-09-2742 · Cited by 47 · see citing works
Self-citationMolecular analysis of iron overload in β2-microglobulin-deficient mice
Muckenthaler, M. U., Rodrigues, P., Macedo, M. G., Miñana, B., Brennan, K., Cardoso, E. M., Hentze, M. W., & de Sousa, M. A. B. (2004) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2004.05.003 · Cited by 42 · see citing works
Unusual MHC-like molecules; CD1, Fc receptor, the hemochromatosis gene product, and viral homologs
Wilson, I. A., & Björkman, P. J. (1998) · Current Opinion in Immunology · doi:10.1016/s0952-7915(98)80034-4 · Cited by 42 · see citing works
Ajioka, R. S., & Kushner, J. P. (2002) · Seminars in Hematology · doi:10.1053/shem.2002.35634 · Cited by 39 · see citing works
Mechanisms of HFE-induced regulation of iron homeostasis: Insights from the W81A HFE mutation
Zhang, A., Davies, P. S., Carlson, H. L., & Enns, C. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1233675100 · Cited by 38 · see citing works
Self-citationHepatic expression of hemochromatosis genes in two mouse strains after phlebotomy and iron overload.
Bondi, A., Valentino, P., Daraio, F., Porporato, P. E., Gramaglia, E., Carturan, S., Gottardi, E. M., Camaschella, C., & Roetto, A. (2005) · PubMed · Cited by 36 · see citing works
Structure and liver cell expression pattern of the HFE gene in the rat
Holmström, P., Dzikaite, V., Hultcrantz, R. W., Melefors, Ö., Eckes, K., Stal, P. I., Kinnman, N., Smedsrød, B. H., Gåfvels, M. E., & Eggertsen, G. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00293-9 · Cited by 29 · see citing works
JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells
Braiterman, L. T., Heffernan, S., Nyasae, L. K., Johns, D. C., See, A. P., Yutzy, R., McNickle, A., Herman, M., Sharma, A., Naik, U. P., et al. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00159.2007 · Cited by 28 · see citing works
Konieczko, E. M., Ralston, A. K., Crawford, A. R., Karpen, S. J., & Crawford, J. M. (1998) · Hepatology · doi:10.1002/hep.510270130 · Cited by 19 · see citing works
Effect of phlebotomy on hepcidin expression in hemojuvelin-mutant mice
Krijt, J., Niederkofler, V., Salie, R., Šefc, L., Pelichovská, T., Vokurka, M., & Nečas, E. (2007) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2007.02.004 · Cited by 18 · see citing works
Kim, D. S., Ahn, S., Yoon, J., Hong, S. H., Kim, K. E., Maurer, R. A., & Park, S. D. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.4.7519724 · Cited by 17 · see citing works
Cherry, J., Nieuwenhuijsen, B. W., Kaftan, E. J., Kennedy, J. D., & Chanda, P. K. (2008) · Journal of Biochemical and Biophysical Methods · doi:10.1016/j.jprot.2007.12.009 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Two to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120 · see citing works
Ganz, T., & Nemeth, E. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.01.014 · Cited by 1,282 · see citing works
Redox- and non-redox-metal-induced formation of free radicals and their role in human disease
Valko, M., Jomová, K., Rhodes, C. J., Kuča, K., & Musílek, K. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1579-5 · Cited by 1,028 · see citing works
Regulation of cellular iron metabolism
Wang, J., & Pantopoulos, K. (2011) · Biochemical Journal · doi:10.1042/bj20101825 · Cited by 986 · see citing works
Hepcidin and iron regulation, 10 years later
Ganz, T. (2011) · Blood · doi:10.1182/blood-2011-01-258467 · Cited by 962 · see citing works
Mechanisms controlling cellular and systemic iron homeostasis
Galy, B., Conrad, M., & Muckenthaler, M. U. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00648-1 · Cited by 808 · see citing works
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787 · see citing works
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724 · see citing works
The Role of Hepcidin in Iron Metabolism
Nemeth, E., & Ganz, T. (2009) · Acta Haematologica · doi:10.1159/000243791 · Cited by 607 · see citing works
Iron Overload in Human Disease
Fleming, R. E., & Ponka, P. (2012) · New England Journal of Medicine · doi:10.1056/nejmra1004967 · Cited by 592 · see citing works
Iron Homeostasis and the Inflammatory Response
Wessling-Resnick, M. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104804 · Cited by 480 · see citing works
Targeting receptor-mediated endocytotic pathways with nanoparticles: Rationale and advances
Xu, S., Olenyuk, B. Z., Okamoto, C. T., & Hamm‐Alvarez, S. F. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.041 · Cited by 469 · see citing works
Hepcidin and disorders of iron metabolism
Ganz, T., & Nemeth, E. (2011) · Annual Review of Medicine · doi:10.1146/annurev-med-050109-142444 · Cited by 466 · see citing works
Regulation of the Iron Homeostatic Hormone Hepcidin
Sangkhae, V., & Nemeth, E. (2017) · Advances in Nutrition · doi:10.3945/an.116.013961 · Cited by 446 · see citing works
Liver iron sensing and body iron homeostasis
Wang, C.-Y., & Babitt, J. L. (2019) · Blood · doi:10.1182/blood-2018-06-815894 · Cited by 360 · see citing works
Nelson, J. E., Wilson, L., Brunt, E. M., Yeh, M. M., Kleiner, D. E., Ünalp–Arida, A., & Kowdley, K. V. (2010) · Hepatology · doi:10.1002/hep.24038 · Cited by 354 · see citing works
Hypoxic regulation of erythropoiesis and iron metabolism
Haase, V. H. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00174.2010 · Cited by 347 · see citing works
Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis
Liu, Q., Davidoff, O., Niss, K., & Haase, V. H. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63924 · Cited by 328 · see citing works
Iron metabolism: pathophysiology and pharmacology
Roemhild, K., von Maltzahn, F., Weiskirchen, R., Knüchel, R., von Stillfried, S. F., & Lammers, T. (2021) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2021.05.001 · Cited by 315 · see citing works
An overview of molecular basis of iron metabolism regulation and the associated pathologies
Silva, B., & Faustino, P. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.03.011 · Cited by 300 · see citing works
Evstatiev, R., & Gasché, C. (2011) · Gut · doi:10.1136/gut.2010.214312 · Cited by 292 · see citing works
Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms
Yang, L., Wang, H., Xiang, Y., Wu, Q., An, P., Jin, X., Liu, W., Huang, X., Li, Y., Yan, S., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00253-0 · Cited by 283 · see citing works
Importance of Iron Chelation in Free Radical-Induced Oxidative Stress and Human Disease
Jomová, K., & Valko, M. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211798072463 · Cited by 271 · see citing works
Lane, D. J. R., & Richardson, D. R. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.07.007 · Cited by 264 · see citing works
A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders
Yiannikourides, A., & Latunde-Dada, G. O. (2019) · Medicines · doi:10.3390/medicines6030085 · Cited by 265 · see citing works
Common variants in TMPRSS6 are associated with iron status and erythrocyte volume
Benyamin, B., Ferreira, M. A. R., Willemsen, G. A. H. M., Gordon, S. D., Middelberg, R. P. S., McEvoy, B. P., Hottenga, J., Henders, A. K., Campbell, M. J., Wallace, L. M., et al. (2009) · Nature Genetics · doi:10.1038/ng.456 · Cited by 254 · see citing works
Genome-wide association study identifies variants in TMPRSS6 associated with hemoglobin levels
Chambers, J. C., Zhang, W., Li, Y., Sehmi, J., Wass, M. N., Zabaneh, D., Hoggart, C. J., Bayele, H. K., McCarthy, M. I., Peltonen, L., et al. (2009) · Nature Genetics · doi:10.1038/ng.462 · Cited by 249 · see citing works
Fuqua, B. K., Vulpe, C. D., & Anderson, G. J. (2012) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2012.03.015 · Cited by 241 · see citing works
The long history of iron in the Universe and in health and disease
Sheftel, A. D., Mason, A. B., & Ponka, P. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.002 · Cited by 234 · see citing works
Molecular Mechanisms of Hepcidin Regulation: Implications for the Anemia of CKD
Babitt, J. L., & Lin, H. Y.-F. (2010) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2009.12.030 · Cited by 236 · see citing works
Hepcidin: regulation of the master iron regulator
Rishi, G., Wallace, D. F., & Subramaniam, V. N. (2015) · Bioscience Reports · doi:10.1042/bsr20150014 · Cited by 223 · see citing works
Anderson, E. R., & Shah, Y. M. (2012) · Comprehensive physiology · doi:10.1002/cphy.c120016 · Cited by 249 · see citing works
Zhao, N., Zhang, A., & Enns, C. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67225 · Cited by 210 · see citing works
Self-citationSingh, N., Haldar, S., Tripathi, A. K., Horback, K., Wong, J., Sharma, D., Beserra, A., Suda, S., Anbalagan, C., Dev, S., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4931 · Cited by 205 · see citing works
Wallace, D. F., Summerville, L., Crampton, E. M., Frazer, D. M., Anderson, G. J., & Subramaniam, V. N. (2009) · Hepatology · doi:10.1002/hep.23198 · Cited by 206 · see citing works
D’Alessio, F., Hentze, M. W., & Muckenthaler, M. U. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.06.015 · Cited by 200 · see citing works
Disorders of iron metabolism. Part 1: molecular basis of iron homoeostasis
Múñoz, M., García‐Erce, J. A., & Remacha, A. F. (2010) · Journal of Clinical Pathology · doi:10.1136/jcp.2010.079046 · Cited by 202 · see citing works
Iron Regulation: Macrophages in Control
Sukhbaatar, N., & Weichhart, T. (2018) · Pharmaceuticals · doi:10.3390/ph11040137 · Cited by 201 · see citing works
The Role of Iron in the Immune Response to Bacterial Infection
Cherayil, B. J. (2011) · Immunologic Research · doi:10.1007/s12026-010-8199-1 · Cited by 191 · see citing works
Sun, C. C., Vaja, V., Babitt, J. L., & Lin, H. Y.-F. (2011) · American Journal of Hematology · doi:10.1002/ajh.23110 · Cited by 181 · see citing works
Zhao, T., Guo, X., & Sun, Y. (2021) · Aging and Disease · doi:10.14336/ad.2020.0912 · Cited by 176 · see citing works
Iron refractory iron deficiency anemia
Falco, L. D., Sánchez, M., Silvestri, L., Kannengiesser, C., Muckenthaler, M. U., Iolascon, A., Gouya, L., Camaschella, C., & Beaumont, C. (2013) · Haematologica · doi:10.3324/haematol.2012.075515 · Cited by 182 · see citing works
A Systems Biology Approach to Iron Metabolism
Chifman, J., Laubenbacher, R., & Torti, S. V. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-2095-2_10 · Cited by 175 · see citing works
Finberg, K. E., Whittlesey, R. L., Fleming, M. D., & Andrews, N. C. (2010) · Blood · doi:10.1182/blood-2009-05-224808 · Cited by 162 · see citing works
Crossing the Iron Gate: Why and How Transferrin Receptors Mediate Viral Entry
Wessling‐Resnick, M. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051749 · Cited by 163 · see citing works
Lanser, L., Fuchs, D., Kurz, K., & Weiß, G. (2021) · Nutrients · doi:10.3390/nu13113732 · Cited by 166 · see citing works
Forejtnikovà, H., Vieillevoye, M., Zermati, Y., Lambert, M., Pellegrino, R. M., Guihard, S., Gaudry, M., Camaschella, C., Lacombe, C., Roetto, A., et al. (2010) · Blood · doi:10.1182/blood-2010-04-281360 · Cited by 152 · see citing works
Nairz, M., Theurl, I., Schroll, A., Theurl, M., Fritsche, G., Lindner, E., Seifert, M., Crouch, M.-L. V., Hantke, K., Akira, S., et al. (2009) · Blood · doi:10.1182/blood-2009-05-223354 · Cited by 146 · see citing works
Molecular mechanisms of normal iron homeostasis
Zhang, A.-S., & Enns, C. A. (2009) · Hematology · doi:10.1182/asheducation-2009.1.207 · Cited by 145 · see citing works
Self-citationMammalian iron transporters: Families SLC11 and SLC40
Montalbetti, N., Simonin, A., Kovács, G., & Hediger, M. A. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.002 · Cited by 147 · see citing works
Bone Morphogenetic Protein Signaling Is Impaired in an Hfe Knockout Mouse Model of Hemochromatosis
Corradini, E., Garuti, C., Montosi, G., Ventura, P., Andriopoulos, B., Lin, H. Y.-F., Pietrangelo, A., & Babitt, J. L. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.06.057 · Cited by 140 · see citing works
McKie, A. T., & Simpson, R. J. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_6 · Cited by 132 · see citing works
HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression
Wu, X.-G., Wang, Y., Wu, Q., Cheng, W. H., Liu, W., Zhao, Y., Mayeur, C., Schmidt, P. J., Yu, P. B., Wang, F., et al. (2014) · Blood · doi:10.1182/blood-2014-01-552281 · Cited by 129 · see citing works
The Liver in Regulation of Iron Homeostasis
Rishi, G., & Subramaniam, V. N. (2017) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00004.2017 · Cited by 124 · see citing works
Systemic iron homeostasis and erythropoiesis
Papanikolaou, G. V., & Pantopoulos, K. (2017) · IUBMB Life · doi:10.1002/iub.1629 · Cited by 122 · see citing works
Iron Metabolism in Nonalcoholic Fatty Liver Disease
Nelson, J. E., Klintworth, H. M., & Kowdley, K. V. (2011) · Current Gastroenterology Reports · doi:10.1007/s11894-011-0234-4 · Cited by 119 · see citing works
Iron homeostasis in breast cancer
Marques, O., da Silva, B. M., Porto, G., & Lopes, C. (2014) · Cancer Letters · doi:10.1016/j.canlet.2014.01.029 · Cited by 115 · see citing works
BMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression
Kautz, L., Meynard, D., Besson‐Fournier, C., Darnaud, V., Saati, T. A., Coppin, H., & Roth, M. (2009) · Blood · doi:10.1182/blood-2009-02-206771 · Cited by 110 · see citing works
Corradini, E., Schmidt, P. J., Meynard, D., Garuti, C., Montosi, G., Chen, S., Vukicevic, S., Pietrangelo, A., Lin, H. Y., & Babitt, J. L. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.07.044 · Cited by 109 · see citing works
Cellular and mitochondrial iron homeostasis in vertebrates
Chen, C., & Paw, B. H. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.01.003 · Cited by 106 · see citing works
Hemojuvelin and bone morphogenetic protein (BMP) signaling in iron homeostasis
Core, A. B., Canali, S., & Babitt, J. L. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00104 · Cited by 107 · see citing works
Corradini, E., Rozier, M., Meynard, D., Odhiambo, A., Lin, H. Y.-F., Feng, Q., Migas, M. C., Britton, R. S., Babitt, J. L., & Fleming, R. E. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.06.077 · Cited by 102 · see citing works
The iron-regulatory hormone hepcidin: A possible therapeutic target?
Rochette, L., Gudjoncik, A., Guénancia, C., Zeller, M., Cottin, Y., & Vergely, C. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.09.004 · Cited by 99 · see citing works
Garrick, M. D., & Garrick, L. M. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.03.018 · Cited by 102 · see citing works
Iron-Sensing Proteins that Regulate Hepcidin and Enteric Iron Absorption
Knutson, M. D. (2010) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104801 · Cited by 96 · see citing works
Iron metabolism: current facts and future decisions
Tandara, L., & Salamunić, I. (2012) · Biochemia Medica · doi:10.11613/bm.2012.034 · Cited by 96 · see citing works
Gardenghi, S., Grady, R. W., & Rivella, S. (2010) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2010.08.003 · Cited by 96 · see citing works
Volke, M., Gale, D. P., Maegdefrau, U., Schley, G., Klanke, B., Bosserhoff, A.-K., Maxwell, P. H., Eckardt, K.-U., & Warnecke, C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007875 · Cited by 93 · see citing works
Regulation of hepcidin expression at high altitude
Talbot, N. P., Lakhal, S., Smith, T. G., Privat, C., Nickol, A. H., Rivera-Ch, M., León-Velarde, F., Dorrington, K. L., Mole, D. R., & Robbins, P. A. (2012) · Blood · doi:10.1182/blood-2011-03-341776 · Cited by 93 · see citing works
Bone morphogenic proteins in iron homeostasis
Xiao, X., Alfaro-Magallanes, V. M., & Babitt, J. L. (2020) · Bone · doi:10.1016/j.bone.2020.115495 · Cited by 88 · see citing works
Regulators of hepcidin expression
Roth, M., Meynard, D., & Coppin, H. (2019) · Vitamins and hormones · doi:10.1016/bs.vh.2019.01.005 · Cited by 84 · see citing works
Genetic mechanisms and modifying factors in hereditary hemochromatosis
Weiss, G. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2009.201 · Cited by 82 · see citing works
Iron Homeostasis and Its Interaction with Prolyl Hydroxylases
Mole, D. R. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2790 · Cited by 80 · see citing works
Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice
Finberg, K. E., Whittlesey, R. L., & Andrews, N. C. (2011) · Blood · doi:10.1182/blood-2010-10-315507 · Cited by 81 · see citing works
Grgurević, L., Christensen, G. L., Schulz, T. J., & Vukičević, S. (2015) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2015.12.009 · Cited by 80 · see citing works
Gill, D., Brewer, C. F., Monori, G., Trégouët, D., Franceschini, N., Giambartolomei, C., Tzoulaki, I., & Dehghan, A. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.012994 · Cited by 81 · see citing works
Poli, M., Luscieti, S., Gandini, V., Maccarinelli, F., Finazzi, D., Silvestri, L., Roetto, A., & Arosio, P. (2010) · Haematologica · doi:10.3324/haematol.2010.027003 · Cited by 81 · see citing works
A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis
Girelli, D., Trombini, P., Busti, F., Campostrini, N., Sandri, M. F., Pelucchi, S., Westerman, M., Ganz, T., Nemeth, E., Piperno, A., et al. (2010) · Haematologica · doi:10.3324/haematol.2010.033449 · Cited by 79 · see citing works
Hepatocyte-targeted HFE and TFR2 control hepcidin expression in mice
Gao, J., Chen, J., Domenico, I. D., Koeller, D. M., Harding, C. O., Fleming, R. E., Koeberl, D. D., & Enns, C. A. (2010) · Blood · doi:10.1182/blood-2009-09-245209 · Cited by 79 · see citing works
Self-citationZumbrennen‐Bullough, K. B., & Babitt, J. L. (2013) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gft443 · Cited by 80 · see citing works
Transferrin is a major determinant of hepcidin expression in hypotransferrinemic mice
Bartnikas, T. B., Andrews, N. C., & Fleming, M. D. (2011) · Blood · doi:10.1182/blood-2010-05-287359 · Cited by 77 · see citing works
Recycling Iron in Normal and Pathological States
Beaumont, C., & Delaby, C. (2009) · Seminars in Hematology · doi:10.1053/j.seminhematol.2009.06.004 · Cited by 78 · see citing works
The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body
Worthen, C., & Enns, C. A. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00034 · Cited by 78 · see citing works
Self-citationRoetto, A., Cunto, F. D., Pellegrino, R. M., Hirsch, E., Azzolino, O., Bondi, A., Defilippi, I., Carturan, S., Miniscalco, B., Riondato, F., et al. (2010) · Blood · doi:10.1182/blood-2009-09-240960 · Cited by 74 · see citing works
Iron metabolism in thalassemia and sickle cell disease
Mariani, R., Trombini, P., Matteo Pozzi, & Piperno, A. (2009) · Mediterranean Journal of Hematology and Infectious Diseases · doi:10.4084/mjhid.2009.006 · Cited by 73 · see citing works
Decreasing TfR1 expression reverses anemia and hepcidin suppression in β-thalassemic mice
Li, H., Choesang, T., Bao, W., Chen, H., Feola, M., Garcia‐Santos, D., Li, J., Sun, S., Follenzi, A., Pham, P., et al. (2017) · Blood · doi:10.1182/blood-2016-09-742387 · Cited by 71 · see citing works
Enns, C. A., Ahmed, R., Wang, J., Ueno, A., Worthen, C., Tsukamoto, H., & Zhang, A.-S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060534 · Cited by 69 · see citing works
Self-citationLatour, C., Besson‐Fournier, C., Meynard, D., Silvestri, L., Gourbeyre, O., Aguilar‐Martinez, P., Schmidt, P. J., Fleming, M. D., Roth, M., & Coppin, H. (2015) · Hepatology · doi:10.1002/hep.28254 · Cited by 66 · see citing works
Ryan, J. D., Ryan, E. M., Fabre, A., Lawless, M. W., & Crowe, J. (2010) · Hepatology · doi:10.1002/hep.23814 · Cited by 66 · see citing works
The bone morphogenetic protein–hepcidin axis as a therapeutic target in inflammatory bowel disease
Wang, L., Trebicka, E., Fu, Y., Ellenbogen, S., Hong, C. C., Babitt, J. L., Lin, H. Y.-F., & Cherayil, B. J. (2011) · Inflammatory Bowel Diseases · doi:10.1002/ibd.21675 · Cited by 66 · see citing works
Advances in understanding the mechanisms of erythropoiesis in homeostasis and disease
Liang, R. H.-S., & Ghaffari, S. (2016) · British Journal of Haematology · doi:10.1111/bjh.14194 · Cited by 66 · see citing works
Molecular basis of iron-loading disorders
Darshan, D., Frazer, D. M., & Anderson, G. J. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001687 · Cited by 63 · see citing works
Expression and function of iron‐regulatory proteins in retina
Gnana‐Prakasam, J. P., Martin, P. M., Smith, S. B., & Ganapathy, V. (2010) · IUBMB Life · doi:10.1002/iub.326 · Cited by 63 · see citing works
Known and potential roles of transferrin in iron biology
Bartnikas, T. B. (2012) · BioMetals · doi:10.1007/s10534-012-9520-3 · Cited by 63 · see citing works
Transferrin iron uptake is stimulated by ascorbate via an intracellular reductive mechanism
Lane, D. J. R., Chikhani, S., Richardson, V., & Richardson, D. R. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.02.010 · Cited by 63 · see citing works
Gelderman, M. P., Baek, J. H., Yalamanoglu, A., Puglia, M., Vallelian, F., Burla, B., Vostal, J., Schaer, D. J., & Buehler, P. W. (2015) · Haematologica · doi:10.3324/haematol.2014.117325 · Cited by 63 · see citing works
Regulation of Iron Homeostasis and Related Diseases
Li, Y., Huang, X., Wang, J., Huang, R., & Wan, D. (2020) · Mediators of Inflammation · doi:10.1155/2020/6062094 · Cited by 64 · see citing works
Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice
Sebastiani, G., & Pantopoulos, K. (2011) · Metallomics · doi:10.1039/c1mt00082a · Cited by 57 · see citing works
Ha, J., Doğuer, Ç., Wang, X., Flores, S. R., & Collins, J. F. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161033 · Cited by 57 · see citing works
Transferrin‐Directed Internalization and Cycling of Transferrin Receptor 2
Chen, J., Wang, J., Meyers, K. R., & Enns, C. A. (2009) · Traffic · doi:10.1111/j.1600-0854.2009.00961.x · Cited by 56 · see citing works
Self-citation
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review