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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“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
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“is.(15,16) A small peptide hormone of 25 amino cids, hepcidin is produced and secreted predomiantly by hepatocytes, circulates in the bloodtream, and is excreted by the kidneys.”
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“Importantly, the amount of iron in macrophages available for erythropoiesis is limited by increased hepcidin levels (17, 26).”
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Kaitha, S. R., Bashir, M. H., & Ali, T. (2015) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v6.i3.62 · Cited by 164
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“Because both iron deficiency and iron overload are harmful to cells and tissues, iron balance is meticulously regulated to meet the body’s iron requirements and to avoid the toxicity associated with iron excess.(2,3) The liver has first-pass access to dietary nutrients and can readily take up an amount of circulating…”
BackgroundEstimating tissue iron burden: current status and future prospects
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“Although a formal review of the proteins and signalling mechanisms involved in somatic iron regulation is beyond the scope of this review (for more comprehensive discussion, see Ganz, 2007), some understanding is useful to place iron monitoring in proper context.”
InfluentialHepcidin, the hormone of iron metabolism, is bound specifically to α-2-macroglobulin in blood
Pešlová, G., Petrák, J., Kuželová, K., Hrdý, I., Halada, P., Kuchel, P. W., Soe-Lin, S., Ponka, P., Šuťák, R., Becker, E., et al. (2009) · Blood · doi:10.1182/blood-2009-01-201590 · Cited by 127
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Maternal serum hepcidin is low at term and independent of cord blood iron status
Rehu, M., Punnonen, K. R. A., Ostland, V. E., Heinonen, S. T., Westerman, M. E., Pulkki, K. J., & Sankilampi, U. (2010) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2010.01479.x · Cited by 122
“Hepcidin inhibits iron efflux from the cells by degrading its exporter ferroportin, which is the sole known iron transporter in humans (7, 8).”
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von Drygalski, A., & Andris, D. A. (2009) · Nutrition in Clinical Practice · doi:10.1177/0884533609332174 · Cited by 123
“The recently discovered peptide hepcidin is responsible for blocking intestinal iron absorption as well as iron release from stores during inflammation.(75) Hepcidin is up-regulated by interleukin-6, which together with other inflammatory cytokines and proteins like tumor necrosis factor-α, von Willebrand factor, C-re…”
BackgroundInhibition of fibroblast growth factor 23 (FGF23) signaling rescues renal anemia
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BackgroundErythropoietin and erythropoiesis
Fried, W. I. (2009) · Experimental Hematology · doi:10.1016/j.exphem.2009.05.010 · Cited by 119
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Deugnier, Y., Brissot, P., & Loréal, O. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.01.014 · Cited by 98
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“phagocytosis, ultimately recycling their iron content, which is used either for the production of new RBCs or stored for future use.(6,20,23) The recycling of RBCs in the spleen and liver provides most of the body’s iron (2025 mg/d),whereas dietary absorption provides only 12 mg/d of iron.”
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Xu, M., Kashanchi, F., Foster, A., Rotimi, J., Turner, W., Gordeuk, V. R., & Nekhai, S. A. (2010) · Retrovirology · doi:10.1186/1742-4690-7-104 · Cited by 70
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“Prokaryotes and eukaryotes have evolved a multitude of exquisite biological systems to acquire, transport and store this molecule (Ganz, 2007; Wandersman & Delepelaire, 2004).”
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“We could not separate iron deficiency from iron dysregulation under the influence of inflammation, because we did not have measurements of soluble transferrin receptor (11) or hepcidin (10).”
BackgroundIron transport & homeostasis mechanisms: their role in health & disease.
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Ward, D. G., Roberts, K., Stonelake, P. S., Goon, P. K. Y., Zampronio, C. G., Martin, A., Johnson, P. J., Iqbal, T. H., & Tselepis, C. (2008) · Proteome Science · doi:10.1186/1477-5956-6-28 · Cited by 62
“Background Hepcidin, a 25-residue peptide hormone, is a key regulator of iron homeostasis [1-3].”
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The ins and outs of mitochondrial iron-loading: the metabolic defect in Friedreich’s ataxia
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“Since Fpn1 is downregulated by decreased cytosolic iron [32], this again supports the idea that the cardiomyocyte was responding to cytosolic iron-deficiency.”
BackgroundInfluentialFrataxin and the molecular mechanism of mitochondrial iron-loading in Friedreich's ataxia
Chiang, S., Kovačević, Ž., Sahni, S., Lane, D. J. R., Merlot, A. M., Kalinowski, D. S., Huang, M. L. H., & Richardson, D. R. (2016) · Clinical Science · doi:10.1042/cs20160072 · Cited by 58
Iron homeostasis and anemia markers in early breast cancer
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Structure–activity relationship of human liver-expressed antimicrobial peptide 2
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Ferristatin II Promotes Degradation of Transferrin Receptor-1 In Vitro and In Vivo
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“Hepcidin interacts with the iron exporter ferroportin to induce its lysosomal degradation, thereby blocking dietary absorption [35] and release of iron stores [69].”
Protein moonlighting in iron metabolism: glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Boradia, V. M., Raje, M., & Raje, C. I. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140220 · Cited by 55
Hepcidin and inflammatory bowel disease: dual role in host defence and iron homoeostasis
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“The target for serum hepcidin is the iron exporter ferroportin 1, which is found in the plasma membranes of most body cells and is found at high concentrations in duodenal enterocytes, macrophages, and hepatocytes.(3,8) The gene that encodes hepcidin is regulated by iron load, anemia, and, in particular, chronic infla…”
BackgroundThe Role of Iron in Alcohol-Mediated Hepatocarcinogenesis
Mueller, S., & Rausch, V. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-09614-8_6 · Cited by 52
[Iron deficiency and overload. Implications in oxidative stress and cardiovascular health].
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Not all DMT1 mutations lead to iron overload
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Sundramoorthy, A. K., Premkumar, B. S., & Gunasekaran, S. (2015) · ACS Sensors · doi:10.1021/acssensors.5b00172 · Cited by 49
Moonlighting cell surface GAPDH recruits Apo Transferrin to effect iron egress from mammalian cells
Sheokand, N., Malhotra, H., Kumar, S., Tillu, V. A., Chauhan, A. S., Raje, C. I., & Raje, M. (2014) · Journal of Cell Science · doi:10.1242/jcs.154005 · Cited by 49
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Haase‐Fielitz, A., Mertens, P. R., Plaß, M., Kuppe, H., Hetzer, R., Westerman, M. E., Ostland, V. E., Prowle, J. R., Bellomo, R., & Haase, M. (2011) · Critical Care · doi:10.1186/cc10339 · Cited by 46
“The hepcidin gene is regulated by iron loading, hypoxia or inflammation [10-12], and its protein is produced by liver and kidney cells [13].”
BackgroundNon-HFE hemochromatosis: Pathophysiological and diagnostic aspects
Bardou‐Jacquet, E., Ali, Z. B., Beaumont-Epinette, M.-P., Loréal, O., Jouanolle, A., & Brissot, P. (2013) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2013.11.003 · Cited by 47
Serum hepcidin but not prohepcidin may be an effective marker for anemia of inflammation (AI)
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Jiang, X., Gao, M., Chen, Y., Liu, J. L., Qi, S., Ma, J., Zhang, Z., & Xu, Y. H. (2016) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2016.02.005 · Cited by 43
Gu, L., Fu, R., Chen, P., Du, N., Chen, S., Mao, D., Chen, B., Mao, F., Khadaroo, P. A., & Jin, Q. (2020) · Obesity Surgery · doi:10.1007/s11695-020-04488-2 · Cited by 44
A fluorescent probe for the Fe3+ ion pool in endoplasmic reticulum in liver cells
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Iron Deficiency, Zinc, Magnesium, Vitamin Deficiencies in Crohn's Disease: Substitute or Not?
Kruis, W., & Nguyen, G. (2016) · Digestive Diseases · doi:10.1159/000443012 · Cited by 42
Troutt, J. S., Butterfield, A. M., & Konrad, R. J. (2013) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.21634 · Cited by 43
“The 25-amino acid active form of hepcidin (hepcidin-25) is the master hormone regulating iron homeostasis in humans (1, 2) Hepcidin-25 is synthesized and secreted by the liver and controls dietary iron absorption and release of hepatic and macrophage iron stores by binding directly to the iron transport protein ferrop…”
BackgroundAnemia and anemia correction: surrogate markers or causes of morbidity in chronic kidney disease?
Vaziri, N. D. (2008) · Nature Reviews Nephrology · doi:10.1038/ncpneph0847 · Cited by 40
“As mentioned above, there are several mechanisms by which oxidative stress and inflammation cause anemia in patients with CKD”
BackgroundWagner, M., Ashby, D. R., Kurtz, C. B., Alam, A., Busbridge, M., Raff, U., Zimmermann, J., Heuschmann, P. U., Wanner, C., & Schramm, L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0123072 · Cited by 42
“Hepcidin is the key-hormone of iron metabolism in ACD [14] and inflammatory processes are not only a cause, but also a symptom of iron dysregulation [30–32].”
BackgroundInfluentialRole of Cellular Iron and Oxygen in the Regulation of HIV-1 Infection
Nekhai, S. A., Kumari, N., & Dhawan, S. (2013) · Future Virology · doi:10.2217/fvl.13.6 · Cited by 40
Cytochrome P450 1B1: A Key Regulator of Ocular Iron Homeostasis and Oxidative Stress
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“Ferroportin is the only known cellular iron efflux transporter in vertebrates, and it is typically expressed in iron-exporting cells, including enterocytes, macrophages, and hepatocytes [59].”
BackgroundA review of select minerals influencing the haematopoietic process
de Oliveira, D. C., Nogueira‐Pedro, A., Santos, E. W., Hastreiter, A. A., da Silva, G. B., Borelli, P., & Fock, R. A. (2018) · Nutrition Research Reviews · doi:10.1017/s0954422418000112 · Cited by 41
“playing high uptake rates for the non-transferrin-bound Fe present when the Fe exceeds the Fe total binding capacity of transferrin((20,21)) (Fig.”
BackgroundValerio, L. G. (2007) · Toxicology Mechanisms and Methods · doi:10.1080/15376510701556690 · Cited by 38
“In human diseases of iron overload, hepcidin thus far appears to be the etiologic factor in most forms of hemochromatosis (Nemeth and Ganz 2006; Ganz 2007), either through mutations in the gene itself or due to mutations in other molecular factors influencing the synthesis of the hormone.”
BackgroundHepcidin in Trauma: Linking Injury, Inflammation, and Anemia
Sihler, K. C., Raghavendran, K., Westerman, M. E., Ye, W., & Napolitano, L. M. (2010) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e3181f066d5 · Cited by 37
Valenzuela‐Muñoz, V., Valenzuela‐Miranda, D., Gonçalves, A. T., Novoa, B., Figueras, A. J., & Gallardo‐Escárate, C. (2020) · Aquaculture · doi:10.1016/j.aquaculture.2020.735058 · Cited by 36
Vitamin C Affects the Expression of Hepcidin and Erythropoietin Receptor in HepG2 Cells
Chiu, P., Ko, S., & Chang, C. (2012) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2011.09.007 · Cited by 34
“Inversely, an iron-rich environment, presence of inflammation, or renal failure will act as an ‘‘iron signal’’ to augment expression of hepcidin.(4,6) Larger EPO doses and parenteral vitamin C have been used to improve renal anemia in uremic patients.”
Background
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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