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rdf:type |
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lifeskim:mentions |
umls-concept:C0021760,
umls-concept:C0034987,
umls-concept:C0530979,
umls-concept:C0871261,
umls-concept:C0966897,
umls-concept:C1514873,
umls-concept:C1546857,
umls-concept:C1556066,
umls-concept:C1619636,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
1
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pubmed:dateCreated |
2007-9-14
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimicrobial Cationic Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/BMP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 4,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GDF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Gdf2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Differentiation Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Differentiation Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Iron,
http://linkedlifedata.com/resource/pubmed/chemical/hepcidin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0007-1048
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
139
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
138-47
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:17854319-Animals,
pubmed-meshheading:17854319-Antimicrobial Cationic Peptides,
pubmed-meshheading:17854319-Base Sequence,
pubmed-meshheading:17854319-Bone Morphogenetic Protein 4,
pubmed-meshheading:17854319-Bone Morphogenetic Proteins,
pubmed-meshheading:17854319-Cell Line,
pubmed-meshheading:17854319-Cloning, Molecular,
pubmed-meshheading:17854319-Gene Expression Regulation,
pubmed-meshheading:17854319-Growth Differentiation Factor 2,
pubmed-meshheading:17854319-Growth Differentiation Factors,
pubmed-meshheading:17854319-Homeostasis,
pubmed-meshheading:17854319-Humans,
pubmed-meshheading:17854319-Interleukin-6,
pubmed-meshheading:17854319-Iron,
pubmed-meshheading:17854319-Liver,
pubmed-meshheading:17854319-Mice,
pubmed-meshheading:17854319-Molecular Sequence Data,
pubmed-meshheading:17854319-Promoter Regions, Genetic,
pubmed-meshheading:17854319-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:17854319-Sequence Alignment,
pubmed-meshheading:17854319-Stimulation, Chemical,
pubmed-meshheading:17854319-Transcription, Genetic
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pubmed:year |
2007
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pubmed:articleTitle |
Different regulatory elements are required for response of hepcidin to interleukin-6 and bone morphogenetic proteins 4 and 9.
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pubmed:affiliation |
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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