Biometals, 2013-12, Vol.26 (6), p.1051-1065
2013
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- Autor(en) / Beteiligte
- Titel
- Friend of GATA and GATA-6 modulate the transcriptional up-regulation of hepcidin in hepatocytes during inflammation
- Ist Teil von
- Biometals, 2013-12, Vol.26 (6), p.1051-1065
- Ort / Verlag
- Dordrecht: Springer Netherlands
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hepcidin is an antimicrobial peptide hormone that plays a central role in the metabolism of iron and its expression in the liver can be induced through two major pathways: the inflammatory pathway, mainly via IL-6; and the iron-sensing pathway, mediated by BMP-6. GATA-proteins are group of evolutionary conserved transcriptional regulators that bind to the consensus motif—WGATAR—in the promoter region. In hepatoma cells, GATA-proteins 4 and 6 in conjunction with the co-factor friend of GATA (FOG) were shown to modulate the transcription of HAMP . However, it is unclear as to which of the GATA-proteins drive the expression of HAMP in vivo. In this study, using in vitro and in vivo approaches, we investigated the relevance of GATA and FOG proteins in the expression of hepcidin following treatment with IL-6 and BMP-6. We found that treatment of Huh7 cells with either IL-6 or BMP-6 increased the HAMP promoter activity. The HAMP promoter activity following treatment with IL-6 or BMP-6 was further increased by co-transfection of the promoter with GATA proteins 4 and 6. However, co-transfection of the HAMP promoter with FOG proteins 1 or 2 repressed the promoter response to treatments with either IL-6 or BMP-6. The effects of both GATA and FOG proteins on the promoter activity in response to IL-6 or BMP-6 treatment were abrogated by mutation of the GATA response element—TTATCT—in the HAMP promoter region −103/−98. In vivo, treatment of mice with lipopolysaccharide led to a transient increase of Gata - 6 expression in the liver that was positively correlated with the expression of hepcidin. Our results indicate that during inflammation GATA-6 is up-regulated in concert with hepcidin while GATA-4 and FOG (1 and 2) are repressed.
- Sprache
- Englisch; Niederländisch
- Identifikatoren
- ISSN: 0966-0844eISSN: 1572-8773DOI: 10.1007/s10534-013-9683-6Titel-ID: cdi_proquest_miscellaneous_1475532661
- Format
- –
- Schlagworte
- Animals, Base Sequence, Biochemistry, Biocompatibility, Biomedical and Life Sciences, Bone Morphogenetic Protein 6 - pharmacology, Cell Biology, Cell Line, Tumor, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Female, GATA4 Transcription Factor - genetics, GATA4 Transcription Factor - metabolism, GATA6 Transcription Factor - genetics, GATA6 Transcription Factor - metabolism, Gene expression, Gene Expression Regulation, Hepatocytes - cytology, Hepatocytes - drug effects, Hepatocytes - metabolism, Hepcidins - agonists, Hepcidins - genetics, Hepcidins - metabolism, Humans, Inflammation - chemically induced, Inflammation - genetics, Inflammation - metabolism, Interleukin-6 - pharmacology, Iron, Life Sciences, Lipopolysaccharides, Liver, Liver - cytology, Liver - drug effects, Liver - metabolism, Medicine/Public Health, Mice, Mice, Inbred C57BL, Microbiology, Molecular Sequence Data, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Peptides, Pharmacology/Toxicology, Plant Physiology, Promoter Regions, Genetic, Protein expression, Signal Transduction, Transcription Factors - genetics, Transcription Factors - metabolism, Transcription, Genetic