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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

Academic Article
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Overview

authors

  • Truksa, J.
  • Peng, H. F.
  • Lee, Pauline
  • Beutler, Ernest

publication date

  • July 2006

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

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.

subject areas

  • Animals
  • Antimicrobial Cationic Peptides
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Cells, Cultured
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors
  • Hepatocytes
  • Hepcidins
  • Histocompatibility Antigens Class I
  • Humans
  • Interleukin-6
  • Lipopolysaccharides
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation
  • Receptors, Transferrin
  • Transforming Growth Factor beta
  • Up-Regulation
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Research

keywords

  • HepG2
  • inflammation
  • iron
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Identity

PubMed Central ID

  • PMC1502450

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0603124103

PubMed ID

  • 16801541
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Additional Document Info

start page

  • 10289

end page

  • 10293

volume

  • 103

issue

  • 27

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