The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6
Open accessAbstract
Recently, it has been suggested that hepcidin, a peptide involved in iron homeostasis, is regulated by bone morphogenetic proteins (BMPs), apparently by binding to hemojuvelin (Hjv) as a coreceptor and signaling through Smad4. We investigate the role of Hfe, Tfr2 (transferrin receptor 2), and IL-6 in BMP2-, BMP4-, and BMP9-stimulated up-regulation of murine hepcidin, because these molecules, like Hjv, are known to be involved in hepcidin signaling. We show that the BMP signaling pathway acts independently of Hfe, Tfr2, and IL-6: The response to BMP2, BMP4, and BMP9 is similar in isolated hepatocytes of wild-type, Hfe −/− , IL-6 −/− , and Tfr2 m mutant mice. The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2. However, in human HepG2 cells, BMP4 and BMP9 are equally potent, whereas BMP2 requires a higher dose to become an effective hepcidin activator. Moreover, all of the tested BMPs are more potent regulators of hepcidin than IL-6 and thus are the most potent known stimulators of hepcidin transcription.
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
“TfR induction was also observed in TNF-α– or IL-1–treated MRC5 human fibroblasts (305)”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [305]
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
Smad transcription factorsPreprint
Massagué, J., Seoane, J., & Wotton, D. (2005) · Genes & Development · doi:10.1101/gad.1350705 · Cited by 2,519
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
New insights into TGF-β–Smad signalling
ten Dijke, P., & Hill, C. S. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.03.008 · Cited by 1,176
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
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
Regulation of hepcidin transcription by interleukin-1 and interleukin-6
Lee, P. L., Peng, H., Gelbart, T., Wang, L., & Beutler, E. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409808102 · Cited by 542
Self-citationHepcidin 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
Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload
Niederkofler, V. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25683 · Cited by 371
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
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 243
Lee, P., Peng, H., Gelbart, T., & Beutler, E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403108101 · Cited by 221
Self-citationRepulsive Guidance Molecule (RGMa), a DRAGON Homologue, Is a Bone Morphogenetic Protein Co-receptor
Babitt, J. L., Zhang, Y. E., Samad, T. A., Xia, Y. Y., Tang, J., Campagna, J. A., Schneyer, A. L., Woolf, C. J., & Lin, H. Y.-F. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503511200 · Cited by 202
Nakamura, K., Shirai, T., Morishita, S., Uchida, S., Saeki-Miura, K., & Makishima, F. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4535 · Cited by 200
Controlling cell fate by bone morphogenetic protein receptors
ten Dijke, P., Korchynskyi, O., Valdimarsdóttir, G., & Goumans, M. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.09.016 · Cited by 199
The disparate role of BMP in stem cell biology
Varga, A. C., & Wrana, J. L. (2005) · Oncogene · doi:10.1038/sj.onc.1208919 · Cited by 198
Miller, A. F., Harvey, S. A. K., Thies, R. S., & Olson, M. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.24.17937 · Cited by 166
Ganz, T. (2004) · Current Opinion in Hematology · doi:10.1097/00062752-200407000-00004 · Cited by 166
Hepcidin inhibits in vitro erythroid colony formation at reduced erythropoietin concentrations
Dallalio, G. A., Law, E., & Means, R. T. (2005) · Blood · doi:10.1182/blood-2005-07-2854 · Cited by 149
Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin
Lee, P. L., Beutler, E., Rao, S. V., & Barton, J. C. (2004) · Blood · doi:10.1182/blood-2004-01-0072 · Cited by 139
Self-citationNicolas, G., Chauvet, C., Viatte, L., Danan, J. L., Bigard, X. A., Devaux, I., Beaumont, C., Kahn, A., & Vaulont, S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci200215686 · Cited by 127
Gambaro, K., Aberdam, É., Virolle, T., Aberdam, D., & Rouleau, M. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401799 · Cited by 94
Biasiotto, G., Belloli, S., Ruggeri, G., Zanella, I., Gerardi, G., Corrado, M., Gobbi, E., Albertini, A., & Arosio, P. (2003) · Clinical Chemistry · doi:10.1373/clinchem.2003.023440 · Cited by 83
Frazer, D. M., Wilkins, S. J., Millard, K. N., McKie, A. T., Vulpe, C. D., & Anderson, G. J. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.05044.x · Cited by 69
Receptor regulated SMADS in TGF beta signaling
Liu, F. (2003) · Frontiers in bioscience · doi:10.2741/1149 · Cited by 58
Means, R. T. (2003) · Blood Reviews · doi:10.1016/s0268-960x(03)00066-3 · Cited by 58
Research works printed but not linked: 1
- 10.1073/pnas.0403108101 · DOI · Paper page
Cited by
Sorted by citations
Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism
Yu, P. B., Hong, C. C., Sachidanandan, C., Babitt, J. L., Deng, D. Y., Hoyng, S. A., Lin, H. Y.-F., Bloch, K. D., & Peterson, R. T. (2007) · Nature Chemical Biology · doi:10.1038/nchembio.2007.54 · Cited by 1,059
High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin
Tanno, T., Bhanu, N. V., Oneal, P. A., Goh, S.-H., Staker, P., Lee, Y. T., Moroney, J. W., Reed, C. H., Luban, N. L., Wang, R.-H., et al. (2007) · Nature Medicine · doi:10.1038/nm1629 · Cited by 854
BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism
Andriopoulos Jr, B., Corradini, E., Xia, Y., Faasse, S. A., Chen, S., Grgurevic, L., Knutson, M. D., Pietrangelo, A., Vukicevic, S., Lin, H. Y., et al. (2009) · Nature Genetics · doi:10.1038/ng.335 · Cited by 769
Forging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623
Lack of the bone morphogenetic protein BMP6 induces massive iron overload
Meynard, D., Kautz, L., Darnaud, V., Canonne-Hergaux, F., Coppin, H., & Roth, M.-P. (2009) · Nature Genetics · doi:10.1038/ng.320 · Cited by 587
Metadata
- Authors
- Truksa, J., Peng, H., Lee, P., & Beutler, E.
- Affiliations
- Scripps Research Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-07-05
- Volume
- 103
- Issue
- 27
- Pages
- 10289-10293
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1502450
- OpenAlex
- W2064708319
- Cited by
- 309
- References
- 26
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 7 · 2023: 10 · 2022: 3 · 2021: 10 · 2020: 3 · 2019: 11 · 2018: 9 · 2017: 10 · 2016: 14 · 2015: 10 · 2014: 16 · 2013: 19 · 2012: 19
- FWCI
- 21.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 53505, R01DK053505)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- hepcidin, bone morphogenetic proteins, BMP-2, BMP4, BMP9, iron homeostasis, hemojuvelin, HFE gene, transferrin receptor 2, interleukin-6, SMAD4, hepatocytes, BMP signaling
- MeSH terms
- Hemochromatosis Protein, Animals, Cells, Cultured, Humans, Lipopolysaccharides, Membrane Proteins, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Receptors, Transferrin, Histocompatibility Antigens Class I, Interleukin-6, Up-Regulation, Transforming Growth Factor beta, Bone Morphogenetic Proteins, Hepatocytes, Antimicrobial Cationic Peptides, Mice, Bone Morphogenetic Protein 2, Growth Differentiation Factors, Bone Morphogenetic Protein 4, Growth Differentiation Factor 2, 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
