The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)
Open accessAbstract
Iron is essential for many biological processes, including oxygen delivery, and its supply is tightly regulated. Hepcidin, a small peptide synthesized in the liver, is a key regulator of iron absorption and homeostasis in mammals. Hepcidin production is increased by iron overload and decreased by anemia and hypoxia; but the molecular mechanisms that govern the hepcidin response to these stimuli are not known. Here we establish that the von Hippel-Lindau/hypoxia-inducible transcription factor (VHL/HIF) pathway is an essential link between iron homeostasis and hepcidin regulation in vivo. Through coordinate downregulation of hepcidin and upregulation of erythropoietin and ferroportin, the VHL-HIF pathway mobilizes iron to support erythrocyte production.
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and several proteins induced by hypoxia such as hypoxia inducible factor-1 (HIF-1) or platelet derived growth factor BB (PDGF-BB) reduce hepcidin expression, thereby enhancing iron delivery for erythropoiesis (Peyssonnaux et al., 2007; Sonnweber et al., 2014).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Peyssonnaux et al., 2007
Experimental — accuracy not yet measuredIn the citing paper
“In particular, HIF effects (via hepcidin) the mobilisation or iron and can cause the expression of inflammatory cytokines such as IL-1, IL-6 and TNF-α [2254-2256] under conditions (hypoxia) where superoxide and peroxide production are likely to be increased, and consequently increases sepsis (in that HIF-knockout mice are resistant to LPS-induced sepsis [2254,2255]).”
From Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases (2009) · cites this paper as [2254]
In the citing paper
“The von Hippel-Lindau/hypoxia-inducible transcription factor (HIF) system also appears to control hepcidin expression, with HIF1␣ acting as a repressor when it binds to the hepcidin promoter.109”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [109]
In the citing paper
“Experimental studies in cultured cells, in animal models and in human subjects have established that hepcidin production is O2-sensitive and involves the HIF pathway.”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [193]
In the citing paper
“Subsequent investigation revealed that Nrf2 and AP1 family transcription factors, in conjunction with transcriptional coactivator p300/CBP, are involved in the activation of the ARE (246, 302, 306, 307)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [246]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Targeting Hypoxia-Inducible Factors for the Treatment of Anemia in Chronic Kidney Disease Patients
Locatelli, F., Fishbane, S. N., Block, G. A., & Macdougall, I. C. (2017) · American Journal of Nephrology · doi:10.1159/000455166 · Cited by 4,836
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
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
Nemeth, 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 1×
“As Albumin-Cre/VHLflox/flox mice exhibit hepatic inflammation and steatosis (21) (Figure 2C), we examined levels of the proinflammatory cytokine IL-6, which is known to stimulate hepcidin expression and may contribute to the anemia of chronic inflammation (5).”
BackgroundDysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis
Makker, J. S., Hanif, A., Bajantri, B., & Chilimuri, S. S. (2015) · Case Reports in Gastroenterology · doi:10.1159/000373883 · Cited by 1,353
Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351
HIF-1 and mechanisms of hypoxia sensing
Semenza, G. L. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00194-0 · Cited by 1,301
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
Self-citationNicolas, 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
Self-citation
Research works printed but not linked: 4
- Gu, 1998, Gene Expr., 7, 205
- Wenger, 1997, Biol. Chem., 378, 609
- Mazure, 2002, Cancer Res., 62, 1158
- Brugnara, 1994, J. Lab. Clin. Med., 123, 660
Cited by
Sorted by citations
Items 601–637 of 637
Impact of the UPR on the expression of relevant genes for cellular iron metabolism
Oliveira, S. J. (2011)
A novel role for aconitase during erythroid development
Talbot, A.-L. (2011) · doi:10.18130/v3f55z
Identification and analysis of genetic and chemical modulators of iron metabolism
Hawula, Z. J. (2021) · Queensland University of Technology · doi:10.5204/thesis.eprints.225904 · Cited by 1
Nelson, J. E., Trinder, D., & Kowdley, K. V. (2010) · Molecular pathology library · doi:10.1007/978-1-4419-7107-4_44
Schuff‐Werner, P. (2010) · Springer eBooks · doi:10.1007/978-3-642-12765-6_9
Ali, S. (2015) · The Egyptian Journal of Internal Medicine · doi:10.4103/1110-7782.159479
Brandt, S., Takala, J. A., & Lepper, P. (2008) · Yearbook of intensive care and emergency medicine · doi:10.1007/978-3-540-77290-3_44
Weiss, M. J. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732587239.793577754
Basina, O., Derova, J., Derovs, A., & Lejniece, S. (2022) · Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences · doi:10.2478/prolas-2022-0088
Kalaivani, P., Lokeshwari, R., Shankar, R., Christan, S. C., & Prabhakaran, R. (2024) · Chemistry of Inorganic Materials · doi:10.1016/j.cinorg.2024.100080
The Fight for Iron: A Central Theme in Host-Pathogen Interactions
Hamad, M. A. (2025) · Springer eBooks · doi:10.1007/978-981-96-1305-2_11
Iron Deficiency and Poor Cognition in Children
Hamad, M. A., & Abdelhaq, M. (2025) · Springer eBooks · doi:10.1007/978-3-031-40858-8_340-1
Verlaguet, J., Balestrino, D., Nakusi, L., Forestier, C., & Vareille-Delarbre, M. (2025) · Cellular Microbiology · doi:10.1155/cmi/6397050
Effects of Daprodustat on Iron Metabolism in Peritoneal Dialysis Patients: An Exploratory Study
Yan, T., Sakai, Y., Kunoki, S., Hirama, A., Kashiwagi, T., & Iwabu, M. (2025) · Blood Purification · doi:10.1159/000548832
Refining our Understanding of Iron Overload Regulation in CIRI: Addressing Misinterpretations
Yao, K., Wang, X., & Jiang, T. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04583-9
Hypoxia Inducible Factors in Alcoholic Liver Disease: A Dissertation
Nath, B. (2009) · eScholarship@UMassChan · doi:10.13028/2t73-hd94
A Switch in Iron Delivery Is Critical for Postnatal Kidney Development
Qiu, A., Viltard, M., Deng, R., Stauber, J., Ghotra, A., Werth, M., Hinze, C., Beenken, A., Shen, T. H., Khan, A., et al. (2026) · Kidney360 · doi:10.34067/kid.0000001064
Role of iron regulatory proteins in the regulation of iron metabolism by nitric oxide
Stys, A. (2011) · theses.fr (ABES) · doi:10.70675/e4192fa6z4401z465fzbe01zd45118568a2f
Surcharges en fer rares d’origine génétique : caractérisation clinique, fonctionnelle, et biologique
Bardou‐Jacquet, E. (2013) · theses.fr (ABES) · doi:10.70675/99eb557fz5edcz4fdezbd26z84ca08eab5aa
Miller, C., Segvich, D. M., Wanner, J., Mahmood, H., Kirschner, K. M., Matz, J. A., Santangelo, S., Wallace, J. M., & Clinkenbeard, E. L. (2026) · Bone · doi:10.1016/j.bone.2026.117867
Le rôle de l'érythroferrone dans la régulation du métabolisme du fer
Sardo, U. (2020) · theses.fr (ABES) · doi:10.70675/d03e67aczc44bz4af9z8fa1zef080668f44f
Régulation du métabolisme du fer et nouvelles stratégies thérapeutiques
Belot, A. (2020) · theses.fr (ABES) · doi:10.70675/14758a3dze368z4da8zbee5z91e1a5d383fa
Bories, G. F. P. (2011) · theses.fr (ABES) · doi:10.70675/81757398zf42fz45dcz8424z3f14e050bfb4
Informative value of iron metabolism proteins in the diagnosis of anemia in chronic kidney disease
Efendieva, G. M. (2025) · Azerbaijan Journal of Physiology · doi:10.59883/ajp.121
Samiee, M. P., Chegini, A., Shahabi, M., & Teimourpour, A. (2026) · Health Science Reports · doi:10.1002/hsr2.72629
Chopra, S., Singh, V. V., Singh, V. K., Verma, S. K., Saxena, S., Kirar, V., Mathur, P., & Singh, S. N. (2026) · International Journal of Biometeorology · doi:10.1007/s00484-026-03257-7
Agrawal, S., Dash, R. J., Jumin, P., Mishra, S., Raghav, S., Samal, S. C., Ramakrishna, B. S., & Ramadass, B. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1836940
Suk, K. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118407
Zhang, H., Zhu, Z., Chen, X., Li, X., & Shan, J. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1862346
The role of Ncb5or in fatty acid metabolism and redox homeostasis
Xu, M. (2011) · KU ScholarWorks (The University of Kansas)
Metadata
- Authors
- Peyssonnaux, C., Zinkernagel, A. S., Schuepbach, R. A., Rankin, E., Vaulont, S., Haase, V. H., Nizet, V., & Johnson, R. S.
- Affiliations
- University of California San Diego (US)
- Scripps Research Institute (US)
- University of Pennsylvania (US)
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2007-07-02
- Volume
- 117
- Issue
- 7
- Pages
- 1926-1932
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1884690
- OpenAlex
- W2116374020
- Cited by
- 639
- References
- 36
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 19 · 2023: 25 · 2022: 26 · 2021: 34 · 2020: 32 · 2019: 18 · 2018: 36 · 2017: 28 · 2016: 31 · 2015: 30 · 2014: 35 · 2013: 39 · 2012: 43
- FWCI
- 33.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA100787)
- National Institute of Allergy and Infectious Diseases (AI060840, R01AI060840)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21DK073467)
- 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
- iron homeostasis, hypoxia-inducible factor, VHL, hepcidin, erythropoietin, ferroportin, iron mobilization, erythropoiesis, anemia, iron overload, hypoxia
- MeSH terms
- Ferroportin, Albumins, Animals, Base Sequence, Homeostasis, Humans, Iron, Liver, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Polycythemia, Promoter Regions, Genetic, Protein Binding, Down-Regulation, Up-Regulation, Gene Deletion, Integrases, Hepatocytes, Antimicrobial Cationic Peptides, Cation Transport Proteins, Mice, Hypoxia-Inducible Factor 1, Von Hippel-Lindau Tumor Suppressor Protein, 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
