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.
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“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]
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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
Research works printed but not linked: 1
- 10.1073/pnas.0403108101 · DOI · Paper page
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Herrera, B. M., van Dinther, M., ten Dijke, P., & Inman, G. J. (2023) · doi:10.1158/0008-5472.c.6500147
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
Caractérisation de BMP9 (Bone Morphogenetic Protein 9), un nouveau biomarqueur de l'angiogenèse ?
Bidart, M. (2012) · theses.fr (ABES) · doi:10.70675/224671deza4d5z423dzb13azb79bb3a18370
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Bardou‐Jacquet, E. (2013) · theses.fr (ABES) · doi:10.70675/99eb557fz5edcz4fdezbd26z84ca08eab5aa
Le syndrome de Rendu-Osler-Weber : aspects génétiques, moléculaires et épidémiologiques
Din, F. A. E. (2015) · theses.fr (ABES) · doi:10.70675/2bea4075z05b5z47d5zbbd3z3f6caf32edd8
Erythroferrone antagonism of BMPs is governed by a composite heparin-binding motif
Mast, E. M., Hok, L., Leach, E., & Thompson, T. B. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113250
Atrazine induces hepatic lipid metabolism disorder via BMP9/SMAD1/5-mediated iron overload
Chuyuan, L., Jiaxin, Z., Zimeng, L., Wang, Z., Qian, H., Haoyan, M., Yang, J., Yue, Q., & Zhang, Y. (2026) · Toxicology · doi:10.1016/j.tox.2026.154612
ALK1 et BMP9 dans le remodelage vasculaire de la génétique humaine aux modèles murins
Ricard, N. (2011) · theses.fr (ABES) · doi:10.70675/05660d01z8dc5z4e9cz8f9czfcaf0b92c01e
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
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