The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Molecular Control of Iron Transport
Abstract
The iron-regulatory hormone hepcidin is a 25-amino acid peptide that is synthesized in hepatocytes. Hepcidin binds to the cellular iron export channel ferroportin and causes its internalization and degradation and thereby decreases iron efflux from iron exporting tissues into plasma. By this mechanism, hepcidin inhibits dietary iron absorption, the efflux of recycled iron from splenic and hepatic macrophages, and the release of iron from storage in hepatocytes. Hepcidin synthesis is stimulated by plasma iron and iron stores and is inhibited by erythropoietic activity, ensuring that extracellular plasma iron concentrations and iron stores remain stable and the erythropoietic demand for iron is met. During inflammation, increased hepcidin concentrations cause iron sequestration in macrophages, resulting in hypoferremia and eventually anemia of inflammation. Hepcidin deficiency plays a central role in most iron overload disorders. The role of hepcidin abnormalities in anemias that are associated with renal disease and in resistance to erythropoietic therapies remains to be elucidated.
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In the citing paper
“and lead to reduced ferroportin surface expression and hypoferremia”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [188]
In the citing paper
“Hepcidin suppresses intestinal iron uptake and release of iron from internal stores by facilitating the degradation and internalization of the only known cellular iron exporter, ferroportin”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [188]
In the citing paper
“lending support to the notion that hepcidin has a key role in the pathogenesis of anemia of chronic disease.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [188]
In the citing paper
“Chronically elevated serum hepcidin levels are frequently associated with inflammatory states”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [188]
In the citing paper
“(interleukin-6 induces hepcidin transcription via JAK/STAT signaling)”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [188]
Citations
Cites
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
Self-citationNemeth, E., Rivera, S., Gabayan, V., Keller, C., Taudorf, S., Pedersen, B. K., & Ganz, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420945 · Cited by 2,650 · cited 9×
“Although the acute hypoferremic response and hepcidin induction both are impaired in IL-6–deficient mice (21), chronic inflammatory stimulation elicits hepcidin even in IL-6–deficient mice (31).”
BackgroundInfluentialSelf-citationHepcidin, a urinary antimicrobial peptide synthesized in the liver
Park, C. H., Valore, E. V., Waring, A. J., & Ganz, T. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008922200 · Cited by 2,168
Self-citationPigeon, 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
Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)80425-6 · Cited by 1,422
Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein
Nemeth, E., Valore, E. V., Territo, M., Schiller, G., Lichtenstein, A., & Ganz, T. (2003) · Blood · doi:10.1182/blood-2002-10-3235 · Cited by 1,417
LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity
Krause, A., Neitz, S., Mägert, H.-J., Schulz, A., Forssmann, W.-G., Schulz-Knappe, P., & Adermann, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01920-7 · Cited by 1,324
The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis
Donovan, A., Lima, C. A., Pinkus, J. L., Pinkus, G. S., Zon, L. I., Robine, S., & Andrews, N. C. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.01.003 · Cited by 1,275
A Novel Mammalian Iron-regulated Protein Involved in Intracellular Iron Metabolism
Abboud, S., & Haile, D. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000713200 · Cited by 1,267
Nicolas, G., Bennoun, M., Devaux, I., Beaumont, C., Grandchamp, B., Kahn, A., & Vaulont, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151179498 · Cited by 1,233
Nicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X., Devaux, I., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215686 · Cited by 1,214
Vulpe, C. D., Kuo, Y.-M., Murphy, T. L., Cowley, L., Askwith, C., Libina, N., Gitschier, J., & Anderson, G. J. (1999) · Nature Genetics · doi:10.1038/5979 · Cited by 1,084
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression
Babitt, J. L., Huang, F. W., Wrighting, D. M., Xia, Y., Sidis, Y., Samad, T. A., Campagna, J. A., Chung, R. T., Schneyer, A. L., Woolf, C. J., et al. (2006) · Nature Genetics · doi:10.1038/ng1777 · Cited by 1,026
Interleukin-6 induces hepcidin expression through STAT3
Wrighting, D. M., & Andrews, N. C. (2006) · Blood · doi:10.1182/blood-2006-06-027631 · Cited by 983
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
Self-citationSevere iron deficiency anemia in transgenic mice expressing liver hepcidin
Nicolas, G., Bennoun, M., Porteu, A., Mativet, S., Beaumont, C., Grandchamp, B., Sirito, M., Sawadogo, M., Kahn, A., & Vaulont, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.072632499 · Cited by 880
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
Identification of an Intestinal Heme Transporter
Shayeghi, M., Latunde-Dada, G. O., Oakhill, J. S., Laftah, A. H., Takeuchi, K., Halliday, N., Khan, Y., Warley, A., McCann, F. E., Hider, R. C., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.025 · Cited by 755
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
A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression
Wang, R.-H., Li, C., Xu, X., Zheng, Y., Xiao, C., Zerfas, P., Cooperman, S., Eckhaus, M., Rouault, T., Mishra, L., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.10.010 · Cited by 614
Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux
Harris, Z. L., Durley, A. P., Man, T. K., & Gitlin, J. D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10812 · Cited by 568
Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS
Kemna, E., Pickkers, P., Nemeth, E., van der Hoeven, H., & Swinkels, D. (2005) · Blood · doi:10.1182/blood-2005-03-1159 · Cited by 498
Knutson, M. D., Oukka, M., Koss, L. M., Aydemir, F., & Wessling-Resnick, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409409102 · Cited by 479
Suppression of hepcidin during anemia requires erythropoietic activity
Pak, M., Lopez, M. A., Gabayan, V., Ganz, T., & Rivera, S. (2006) · Blood · doi:10.1182/blood-2006-06-028787 · Cited by 472
Self-citationHepcidin in iron overload disorders
Papanikolaou, G., Tzilianos, M., Christakis, J. I., Bogdanos, D., Tsimirika, K., MacFarlane, J., Goldberg, Y. P., Sakellaropoulos, N., Ganz, T., & Nemeth, E. (2005) · Blood · doi:10.1182/blood-2004-12-4844 · Cited by 445
Hunter, H. N., Fulton, D. B., Ganz, T., & Vogel, H. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205305200 · Cited by 400
Hepcidin is decreased in TFR2 hemochromatosis
Nemeth, E., Roetto, A., Garozzo, G., Ganz, T., & Camaschella, C. (2004) · Blood · doi:10.1182/blood-2004-08-3042 · Cited by 399
Iron Metabolism in the Reticuloendothelial System
Knutson, M. D., & Wessling‐Resnick, M. (2003) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/713609210 · Cited by 360
Iron, Infections, and Anemia of Inflammation
Jurado, R. L. (1997) · Clinical Infectious Diseases · doi:10.1086/515549 · Cited by 358
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
Truksa, J., Peng, H., Lee, P., & Beutler, E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603124103 · Cited by 309
Rivera, S., Nemeth, E., Gabayan, V., Lopez, M. A., Farshidi, D., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2005-04-1766 · Cited by 308
Self-citationMuckenthaler, 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 295
Detection of serum hepcidin in renal failure and inflammation by using ProteinChip System
Tomosugi, N., Kawabata, H., Wakatabe, R., Higuchi, M., Yamaya, H., Umehara, H., & Ishikawa, I. (2006) · Blood · doi:10.1182/blood-2005-10-4043 · Cited by 293
Nemeth, E., Preza, G. C., Jung, C.-L., Kaplan, J., Waring, A. J., & Ganz, T. (2006) · Blood · doi:10.1182/blood-2005-05-2049 · Cited by 273
Self-citationResistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin
Drakesmith, H., Schimanski, L. M., Ormerod, E., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., et al. (2005) · Blood · doi:10.1182/blood-2005-02-0561 · Cited by 264
Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis
Vokurka, M., Krijt, J., Šulc, K., & Nečas, E. (2006) · Physiological Research · doi:10.33549/physiolres.930841 · Cited by 263
Craven, C. M., Alexander, J., Eldridge, M., Kushner, J. P., Bernstein, S., & Kaplan, J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.10.3457 · Cited by 259
Kulaksiz, H., Gehrke, S. G., Janetzko, A., Rost, D., Bruckner, T., Kallinowski, B., & Stremmel, W. (2004) · Gut · doi:10.1136/gut.2003.022863 · Cited by 247
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 246
The molecular basis of ferroportin-linked hemochromatosis
De Domenico, I., Ward, D. M., Nemeth, E., Vaughn, M. B., Musci, G., Ganz, T., & Kaplan, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0503804102 · Cited by 230
Self-citationIn vitro functional analysis of human ferroportin (FPN) and hemochromatosis-associated FPN mutations
Schimanski, L. M., Drakesmith, H., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., Robson, K. J. H., et al. (2005) · Blood · doi:10.1182/blood-2004-11-4502 · Cited by 212
Iron Imports. II. Iron uptake at the apical membrane in the intestine
Mackenzie, B., & Garrick, M. D. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00363.2005 · Cited by 211
Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia
Rivera, S., Liu, L., Nemeth, E., Gabayan, V., Sorensen, O. E., & Ganz, T. (2005) · Blood · doi:10.1182/blood-2004-08-3375 · Cited by 196
Self-citationDétivaud, L., Nemeth, E., Boudjéma, K., Turlin, B., Troadec, M., Leroyer, P., Ropert, M., Jacquelinet, S., Courselaud, B., Ganz, T., et al. (2005) · Blood · doi:10.1182/blood-2004-12-4855 · Cited by 191
Theurl, I., Mattle, V., Seifert, M., Mariani, M., Marth, C., & Weiss, G. (2006) · Blood · doi:10.1182/blood-2005-08-3364 · Cited by 188
Regulation of hepcidin and ferroportin expression by lipopolysaccharide in splenic macrophages
Liu, X.-B., Nguyen, N.-B., Marquess, K. D., Yang, F., & Haile, D. J. (2005) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2005.04.006 · Cited by 186
Urinary hepcidin in congenital chronic anemias
Kearney, S. L., Nemeth, E., Neufeld, E. J., Thapa, D., Ganz, T., Weinstein, D. A., & Cunningham, M. J. (2007) · Pediatric Blood & Cancer · doi:10.1002/pbc.20616 · Cited by 172
Self-citationSham, R. L., Phatak, P. D., West, C., Lee, P., Andrews, C., & Beutler, E. (2005) · Blood Cells, Molecules, and Diseases · doi:10.1016/j.bcmd.2004.12.002 · Cited by 146
Functional consequences of ferroportin 1 mutations
Liu, X.-B., Yang, F., & Haile, D. J. (2005) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2005.04.005 · Cited by 136
Novel urine hepcidin assay by mass spectrometry
Kemna, E., Tjalsma, H., Laarakkers, C. M., Nemeth, E., Willems, H. L., & Swinkels, D. W. (2005) · Blood · doi:10.1182/blood-2005-05-1873 · Cited by 135
Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice
Viatte, L., Lesbordes, J.-C., Lou, D.-Q., Bennoun, M., Nicolas, G., Kahn, A., Canonne‐Hergaux, F., & Vaulont, S. (2005) · Blood · doi:10.1182/blood-2004-12-4608 · Cited by 119
Iron overload due to mutations in ferroportin.
Domenico, I. D., Ward, D. M., Musci, G., & Kaplan, J. (2006) · PubMed · Cited by 84
Viatte, L. (2005) · Blood · doi:10.1182/blood-2005-10-4071 · Cited by 81
Means, R. T., & Krantz, S. B. (1996) · PubMed · Cited by 54
Intravenous iron supplementation in the anaemia of renal and cardiac failure—a double-edged sword?
Slotki, I. N. (2005) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh1102 · Cited by 21
In Chronic Inflammation, There Exists an IL-6 Independent Pathway for the Induction of Hepcidin.
Rivera, S., Gabayan, V. R., & Ganz, T. (2004) · Blood · doi:10.1182/blood.v104.11.3205.3205 · Cited by 11
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Delayed Graft Function in the Kidney Transplant
Siedlecki, A. M., Irish, W. D., & Brennan, D. C. (2011) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03754.x · Cited by 823
“Collectively oxygen free radicals disrupt intracellular metabolic processes, transcellular solute gradients, and the proximal tubular cell super structure (23).”
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Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787
“Hepcidin suppresses intestinal iron uptake and release of iron from internal stores by facilitating the degradation and internalization of the only known cellular iron exporter, ferroportin, which is expressed on the surface of enterocytes, hepatocytes and macrophages.(187) In iron-deficient states (e.”
BackgroundRichardson, D. R., Lane, D. J. R., Becker, E. M., Huang, M. L.-H., Whitnall, M., Rahmanto, Y. S., Sheftel, A. D., & Ponka, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912925107 · Cited by 536
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“Recently, hepcidin has emerged as the master regulator of iron availability to the bone marrow (Ganz, 2007).”
BackgroundClark, S. F. (2008) · Nutrition in Clinical Practice · doi:10.1177/0884533608314536 · Cited by 392
Metadata
- Authors
- Ganz, T.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Ganz, Tomas
- ORCID
- Ganz, Tomas
- Venue
- Journal of the American Society of Nephrology
- Published
- 2007-02
- Volume
- 18
- Issue
- 2
- Pages
- 394-400
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2120359196
- Cited by
- 353
- References
- 58
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 8 · 2023: 9 · 2022: 15 · 2021: 30 · 2020: 13 · 2019: 17 · 2018: 17 · 2017: 12 · 2016: 19 · 2015: 22 · 2014: 17 · 2013: 22 · 2012: 18
- FWCI
- 23.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL046809, HL46809)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hepcidin, iron transport, ferroportin, iron homeostasis, dietary iron absorption, iron storage, erythropoiesis, inflammation, anemia of chronic disease, iron overload, anemia of chronic kidney disease
- MeSH terms
- Ferroportin, Anemia, Biological Transport, Bone and Bones, Homeostasis, Humans, Inflammation, Intestinal Absorption, Iron, Kidney Diseases, Kinetics, Liver, Iron Overload, Antimicrobial Cationic Peptides, Cation Transport Proteins, Hepcidins
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