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Different regulatory elements are required for response of hepcidin to interleukin-6 and bone morphogenetic proteins 4 and 9

Academic Article
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Overview

authors

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

publication date

  • October 2007

journal

  • British Journal of Haematology  Journal

abstract

  • Hepcidin is a major regulator of iron homeostasis. Hepcidin expression is upregulated by inflammatory cytokines, particularly interleukin (IL)-6 and even more potently by the bone morphogenetic proteins 2, 4 and 9 (BMP-2, BMP-4 and BMP-9). This study showed that the regulation of hepcidin expression by IL-6 and BMPs occurs through distinct regulatory elements. The induction of hepcidin by BMPs requires at least two regions of the Hamp1 promoter, one between 140-260 bp and the other between 1.6-2.0 kb upstream of the start of translation. Reporter constructs including 1.6-2.0 kb of the Hamp1 promoter were induced >16-fold by BMPs whereas a 260 bp reporter Hamp1 promoter construct was induced only two- to threefold. The distal 1.6-2.0 kb region appeared to contain several different BMP-responsive elements, as incremental lengthening of the promoter construct in this region produced gradual escalation of BMP-responsiveness. In contrast, the IL-6 response required only the proximal 260 bp Hamp1 promoter region. Furthermore, there were no regulatory elements located in the non-coding or coding regions of Hamp1 and activation of the Hamp1 promoter was absent or markedly reduced in cells of non-hepatic origin.

subject areas

  • Animals
  • Antimicrobial Cationic Peptides
  • Base Sequence
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Cell Line
  • Cloning, Molecular
  • Gene Expression Regulation
  • Growth Differentiation Factor 2
  • Growth Differentiation Factors
  • Hepcidins
  • Homeostasis
  • Humans
  • Interleukin-6
  • Iron
  • Liver
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Regulatory Sequences, Nucleic Acid
  • Sequence Alignment
  • Stimulation, Chemical
  • Transcription, Genetic
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Research

keywords

  • cytokine
  • iron
  • mouse
  • regulation
  • transcription
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Identity

International Standard Serial Number (ISSN)

  • 0007-1048

Digital Object Identifier (DOI)

  • 10.1111/j.1365-2141.2007.06728.x

PubMed ID

  • 17854319
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Additional Document Info

start page

  • 138

end page

  • 147

volume

  • 139

issue

  • 1

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