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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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 observed in TNF-α- or IL-1-treated MRC5 human fibroblasts.
“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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- 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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