DOI: 10.1111/j.1365-2141.2007.06728.x. Different regulatory elements are required for response of hepcidin to interleukin‐6 and bone morphogenetic proteins 4 and 9

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

10.1111/j.1365-2141.2007.06728.x

Crossref journal-article

Wiley

British Journal of Haematology (311)

Abstract

SummaryHepcidin 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.

Bibliography

Truksa, J., Peng, H., Lee, P., & Beutler, E. (2007). Different regulatory elements are required for response of hepcidin to interleukinâ6 and bone morphogenetic proteins 4 and 9. British Journal of Haematology, 139(1), 138â147. Portico.

Authors 4

Jaroslav Truksa (first)
Hongfan Peng (additional)
Pauline Lee (additional)
Ernest Beutler (additional)

References 17 Referenced 53

10.1093/emboj/16.3.495
10.1038/ng1777
10.1016/j.bcmd.2007.01.004
10.1111/j.1365-2141.2004.05044.x
10.1182/asheducation-2006.1.29
10.1074/jbc.C600197200
10.1038/sj.onc.1205681
10.1002/jcb.10299
10.1016/j.jhep.2004.02.029 / Journal of Hepatology / Different expression pattern of hepcidin genes in the liver and pancreas of C57BL/6N and DBA/2N mice by Krijt J. (2004)
10.1073/pnas.0403108101
10.1073/pnas.0409808102
10.1146/annurev.nutr.26.061505.111303
10.1172/JCI0215686
10.1093/nar/23.23.4907
10.1073/pnas.0603124103
10.1016/j.cmet.2005.10.010
10.1182/blood-2006-06-027631

Dates

Type	When
Created	17 years, 11 months ago (Sept. 16, 2007, 1 a.m.)
Deposited	1 year, 10 months ago (Oct. 15, 2023, 8:54 a.m.)
Indexed	1 year ago (Aug. 15, 2024, 11:48 a.m.)
Issued	17 years, 11 months ago (Sept. 11, 2007)
Published	17 years, 11 months ago (Sept. 11, 2007)
Published Online	17 years, 11 months ago (Sept. 11, 2007)
Published Print	17 years, 11 months ago (Oct. 1, 2007)

Funders 0

None

BibTeX

@article{Truksa_2007, title={Different regulatory elements are required for response of hepcidin to interleukin‐6 and bone morphogenetic proteins 4 and 9}, volume={139}, ISSN={1365-2141}, url={http://dx.doi.org/10.1111/j.1365-2141.2007.06728.x}, DOI={10.1111/j.1365-2141.2007.06728.x}, number={1}, journal={British Journal of Haematology}, publisher={Wiley}, author={Truksa, Jaroslav and Peng, Hongfan and Lee, Pauline and Beutler, Ernest}, year={2007}, month=sep, pages={138–147} }

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