The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
C/EBPα Regulates Hepatic Transcription of Hepcidin, an Antimicrobial Peptide and Regulator of Iron Metabolism
Open accessAbstract
Originally identified as a gene up-regulated by iron overload in mouse liver, the HEPC gene encodes hepcidin, the first mammalian liver-specific antimicrobial peptide and potential key regulator of iron metabolism. Here we demonstrate that during rat liver development, amounts of HEPC transcripts were very low in fetal liver, strongly and transiently increased shortly after birth, and reappeared in adult liver. To gain insight into mechanisms that regulate hepatic expression of hepcidin, 5'-flanking regions of human and mouse HEPC genes were isolated and analyzed by functional and DNA binding assays. Human and mouse HEPC promoter-luciferase reporter vectors exhibited strong basal activity in hepatoma HuH-7 and mouse hepatocytes, respectively, but not in non-hepatic U-2OS cells. We found that CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPbeta were respectively very potent and weak activators of both human and mouse promoters. In contrast, co-expression of hepatocyte nuclear factor 4alpha (HNF4alpha) failed to induce HEPC promoter activity. By electrophoretic mobility shift assay we demonstrated that one putative C/EBP element found in the human HEPC promoter (-250/-230) predominantly bound C/EBPalpha from rat liver nuclear extracts. Hepatic deletion of the C/EBPalpha gene resulted in reduced expression of HEPC transcripts in mouse liver. In contrast, amounts of HEPC transcripts increased in liver-specific HNF4alpha-null mice. Decrease of hepcidin mRNA in mice lacking hepatic C/EBPalpha was accompanied by iron accumulation in periportal hepatocytes. Finally, iron overload led to a significant increase of C/EBPalpha protein and HEPC transcripts in mouse liver. Taken together, these data demonstrate that C/EBPalpha is likely to be a key regulator of HEPC gene transcription and provide a novel mechanism for cross-talk between the C/EBP pathway and iron metabolism.
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?
In the citing paper
“when HeLa cells stably transfected with tetracycline-inducible ferritin H and L were forced to overexpress ferritin, the accumulation of H2O2-induced ROS was reduced (59).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [59]
In the citing paper
“Accumulating evidence shows that ferritin acts as an antioxidant protein (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [59]
In the citing paper
“overexpression or knockdown of ferritin expression in mammalian cells has proven the cytoprotective role of ferritin under prooxidative conditions (59, 60, 78, 159, 227, 243).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [59]
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
Quandt, K., Frech, K., Karas, H., Wingender, E., & Werner, T. (1995) · Nucleic Acids Research · doi:10.1093/nar/23.23.4878 · Cited by 2,587
Phylogenetic Perspectives in Innate Immunity
Hoffmann, J. A., Kafatos, F. C., Janeway, C. A., & Ezekowitz, R. A. B. (1999) · Science · doi:10.1126/science.284.5418.1313 · Cited by 2,524
Hepcidin, 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
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
Self-citationNormal growth and development in the absence of hepatic insulin-like growth factor I
Yakar, S., Liu, J., STANNARD, B. S., Butler, A. A., Accili, D., Sauer, B., & LeRoith, D. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7324 · Cited by 1,418
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 role of cationic antimicrobial peptides in innate host defences
Hancock, R. E. W., & Diamond, G. (2000) · Trends in Microbiology · doi:10.1016/s0966-842x(00)01823-0 · Cited by 1,233
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
Tissue-specific in vitro transcription from the mouse albumin promoter
Gorski, K., Carneiro, M., & Schibler, U. (1986) · Cell · doi:10.1016/0092-8674(86)90519-2 · Cited by 1,227
Hayhurst, G. P., Lee, Y.-H., Lambert, G., Ward, J. M., & Gonzalez, F. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1393-1403.2001 · Cited by 1,107
Self-citation
Research works printed but not linked: 2
- Ryden, 1989, Mol. Cell. Biol., 9, 1155
- Lee, 1994, Mol. Cell. Biol., 14, 1383
Cited by
Sorted by citations
Items 201–244 of 244
REVIEW PAPER An overall view of the process of the regulation of human iron metabolism
Formanowicz, D., & Formanowicz, P. (2014) · Biotechnologia · doi:10.5114/bta.2011.46534 · Cited by 7
Hepcidin, show some self-control! How the hormone of iron metabolism regulates its own expression
Lane, D. J. R., Huang, M. L. H., & Richardson, D. R. (2013) · Biochemical Journal · doi:10.1042/bj20130358 · Cited by 6
Hino, K., & Harada, M. (2016) · Springer eBooks · doi:10.1007/978-4-431-55790-6_7 · Cited by 6
Chalaya, T. V., Акопов, С. Б., Николаев, Л. Г., & Sverdlov, E. D. (2006) · Biochemistry (Moscow) · doi:10.1134/s0006297906030096 · Cited by 6
Physiopathologie et génétique de l'hémochromatose HFE de type 1
Loréal, O., Ropert, M., Mosser, A., Déhais, V., Deugnier, Y., David, V., Brissot, P., & Jouanolle, A. (2007) · La Presse Médicale · doi:10.1016/j.lpm.2007.03.038 · Cited by 7
Self-citationHNF-4alpha Negatively Regulates Hepcidin Expression Through BMPR1A in HepG2 Cells
Shi, W., Wang, H., Zheng, X., Jiang, X., Xu, Z. Q., Shen, H., & Li, M. (2016) · Biological Trace Element Research · doi:10.1007/s12011-016-0846-5 · Cited by 5
Molecular Effects of Alcohol on Iron Metabolism
Mehta, K. J., Farnaud, S., & Patel, V. B. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800773-0.00028-8 · Cited by 5
Boden, G. H., Scapa, E. F., Kanno, K., Cohen, D. E., Brosnan, M. E., Brosnan, J. T., Pessayre, D., Roy‐Chowdhury, N., Lu, Y., Roy‐Chowdhury, J., et al. (2007) · Wiley eBooks · doi:10.1002/9780470691861.ch2c · Cited by 5
Actualités sur l’hémochromatose
Loréal, O., Lan, C. L., Troadec, M., Guyader, D., & Brissot, P. (2004) · Gastroentérologie Clinique et Biologique · doi:10.1016/s0399-8320(04)94993-7 · Cited by 4
Self-citationThe human iron exporter ferroportin. Insight into the transport mechanism by molecular modeling
Tortosa, V., di Patti, M. C. B., Musci, G., & Polticelli, F. (2015) · Bio-Algorithms and Med-Systems · doi:10.1515/bams-2015-0034 · Cited by 4
Maltaneri, R. E., Chamorro, M. E., Gionco, S., Nesse, A. B., & Vittori, D. C. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2024.119800 · Cited by 3
Hepcidin: A multifaceted hormone in iron homeostasis and tumor biology
Liu, X., Zhang, X., Fan, Y., & Tan, K. (2024) · Vitamins and hormones · doi:10.1016/bs.vh.2024.10.003 · Cited by 2
Key Transcription Factors: Avenue for Treating Alcoholic Liver Disease
Guo, M., Cao, J.-N., Li, X., & Jin, L. (2025) · Current Medical Science · doi:10.1007/s11596-025-00079-3 · Cited by 2
Disorders of Red Cell Production and the Iron-Loading Anemias
Rivella, S. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_16 · Cited by 2
Oliveras, A., & Espel, E. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2007.07.021 · Cited by 2
The effect of amino acid deprivation on the transfer of iron through Caco-2 cell monolayers
Roussel, G., Stevens, V. J., Cottin, S., & McArdle, H. J. (2017) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2016.12.016 · Cited by 2
Bail, A. L. (2009) · Cited by 2
Isolation of Novel Hepcidin Isoforms from the Rockbream Oplegnathus fasciatus (Perciformes)
Lee, S.-Y., & Nam, Y.-K. (2011) · Fisheries and aquatic sciences · doi:10.5657/fas.2011.14.1.031 · Cited by 1
Crawford, D. H., Fletcher, L. M., & Kowdley, K. V. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_22 · Cited by 1
Pietrangelo, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-37591-7.00060-4 · Cited by 1
Okazaki, Y., & Glass, J. (2017) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2017.02.007 · Cited by 1
Liver Cirrhosis with Inherited Liver Disease: Hemochromatosis
Hino, K., & Nishina, S. (2019) · Springer eBooks · doi:10.1007/978-981-13-7979-6_4 · Cited by 1
Iron in mammals: pathophysiological mechanisms of overload and deficiency in relation to disease
Johnson, M. B., Enns, C. A., & Zhang, A. (2005) · Topics in current genetics · doi:10.1007/4735_99 · Cited by 1
A Glimpse of Future Hepatitis C Virus Treatment Paradigms
Terrault, N. A., & Khalili, M. (2010) · Hepatology · doi:10.1002/hep.23523 · Cited by 1
Panton, N. (2008) · SUNScholar (Stellenbosch University) · Cited by 1
Iron-Regulatory Function of Hepcidin in the Channel Catfish and Western Clawed Frog
Hu, X. (2008) · Cited by 1
The Role of Hypoxia-Inducible Factors in the Regulation of Systemic Iron Homeostasis.
Anderson, E. R. (2013) · Deep Blue (University of Michigan)
Hemochromatosis associated with hepcidin gene (HAMP) mutations
Barton, J. C., Edwards, C. Q., Phatak, P. D., Britton, R. S., & Bacon, B. R. (2010) · Cambridge University Press eBooks · doi:10.1017/cbo9780511777035.016
IRON HOMEOSTASIS IN IMMUNE MONONUCLEAR CELLS: A POTENTIAL ROLE IN ATHEROGENESIS
Marques, L. (2015) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.13140/rg.2.2.24210.40643
Iron Homeostasis: Hepcidin Regulation
Camaschella, C., & Silvestri, L. (2004) · Wiley eBooks · doi:10.1002/9781119951438.eibc2131
Lipiński, P., Styś, A., & Starzyński, R. R. (2012)
Hepcidin Activation During Inflammation: Make It STAT
Pietrangelo, A., Dierssen, U., Valli, L., Rump, A., Corradini, E., & Klein, C. (2007)
Li, X., Wang, G., & Li, J. (2012) · Hereditas (Beijing) · doi:10.3724/sp.j.1005.2012.01456
Impact of the UPR on the expression of relevant genes for cellular iron metabolism
Oliveira, S. J. (2011)
Genetic Testing for Disorders of Iron Homeostasis
Barton, J. C., Lee, P. L., & Edwards, C. Q. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_26
Evaluation of some hormones in patients with major β-Thalassemia in the Nineveh Governorate - Iraq
Al-Azzawie, Z. Z. I., & Jankeer, M. H. (2024) · Acta Scientiarum Animal Sciences · doi:10.4025/actascianimsci.v46i1.70358
Computational Analysis of Iron-binding Proteins in the Mutational Landscape of Cancer
Chauhan, S., Kulharia, M., & Verma, S. K. (2025) · Biological Trace Element Research · doi:10.1007/s12011-025-04881-x
Surcharges en fer rares d’origine génétique : caractérisation clinique, fonctionnelle, et biologique
Bardou‐Jacquet, E. (2013) · theses.fr (ABES) · doi:10.70675/99eb557fz5edcz4fdezbd26z84ca08eab5aa
Mutation HFE et performance physique
Djemai, H. (2018) · theses.fr (ABES) · doi:10.70675/d4e9c367zc7faz4ffbzb60cz3664ac9214ca
Cao, F., Ge, X., Pi, A., Huang, Q., Pei, L., Chen, R., Cao, W., Ding, Q., Yang, M., Song, Q., et al. (2026) · Communications Biology · doi:10.1038/s42003-026-10398-3
Metadata
- Authors
- Courselaud, B., Pigeon, C., Inoue, Y., Inoue, J., Gonzalez, F. J., Leroyer, P., Gilot, D., Boudjema, K., Guguen-Guillouzo, C., Brissot, P., Loréal, O., & Ilyin, G.
- Affiliations
- Inserm (FR)
- National Institutes of Health (US)
- Corresponding author
- Ilyin, Gennady
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 277
- Issue
- 43
- Pages
- 41163-41170
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2172197126
- Cited by
- 245
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 6 · 2015: 14 · 2014: 7 · 2013: 21 · 2012: 14
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ligue Contre le Cancer
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- hepcidin, C/EBPα, C/EBPβ, HNF4α, iron metabolism, liver development, transcriptional regulation, promoter analysis, iron overload, iron accumulation, hepatocytes, antimicrobial peptides
- MeSH terms
- Animals, Anti-Bacterial Agents, Base Sequence, DNA, Female, Gene Expression Regulation, Humans, Iron, Liver, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger, Transcription, Genetic, Rats, Sprague-Dawley, CCAAT-Enhancer-Binding Protein-alpha, Antimicrobial Cationic Peptides, Mice, Rats, 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
