Cited by 309Iron Metabolism and DisordersTGF-β signaling in diseasesPlant Micronutrient Interactions and Effects

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Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6

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Truksa, Jaroslav, Peng, Hongfan, Lee, Pauline, Beutler, Ernest·2006·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0603124103PMC PMC1502450

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Abstract

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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Authors: Truksa, J., Peng, H., Lee, P., & Beutler, E.
Affiliations: Scripps Research Institute (US)
ORCID: Truksa, Jaroslav
Lee, Pauline
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
DOI: 10.1073/pnas.0603124103
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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Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6

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