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BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin

Gibert, Yann, Lattanzi, Victoria J., Zhen, Aileen W., Vedder, Lea, Brunet, Frederic, Fasse, Sarah A., Babitt, Jodie L., Lin, Herbert Y., Hammerschmidt, Matthias and Fraenkel, Paula G. 2011, BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin, PLoS one, vol. 6, no. 1, pp. 1-14, doi: 10.1371/journal.pone.0014553.

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Title BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin
Formatted title BMP signaling modulates Hepcidin expression in zebrafish embryos independent of Hemojuvelin
Author(s) Gibert, Yann
Lattanzi, Victoria J.
Zhen, Aileen W.
Vedder, Lea
Brunet, Frederic
Fasse, Sarah A.
Babitt, Jodie L.
Lin, Herbert Y.
Hammerschmidt, Matthias
Fraenkel, Paula G.
Journal name PLoS one
Volume number 6
Issue number 1
Article ID e14553
Start page 1
End page 14
Total pages 14
Publisher Public Library of Science
Place of publication San Francisco, California
Publication date 2011-01
ISSN 1932-6203
Keyword(s) hemojuvelin (Hjv)
hepcidin expression
bone morphogenetic protein (BMP) signaling
zebrafish embryo
Summary Hemojuvelin (Hjv), a member of the repulsive-guidance molecule (RGM) family, upregulates transcription of the iron regulatory hormone hepcidin by activating the bone morphogenetic protein (BMP) signaling pathway in mammalian cells. Mammalian models have identified furin, neogenin, and matriptase-2 as modifiers of Hjv's function. Using the zebrafish model, we evaluated the effects of hjv and its interacting proteins on hepcidin expression during embryonic development. We found that hjv is strongly expressed in the notochord and somites of the zebrafish embryo and that morpholino knockdown of hjv impaired the development of these structures. Knockdown of hjv or other hjv-related genes, including zebrafish orthologs of furin or neogenin, however, failed to decrease hepcidin expression relative to liver size. In contrast, overexpression of bmp2b or knockdown of matriptase-2 enhanced the intensity and extent of hepcidin expression in zebrafish embryos, but this occurred in an hjv-independent manner. Furthermore, we demonstrated that zebrafish hjv can activate the human hepcidin promoter and enhance BMP responsive gene expression in vitro, but is expressed at low levels in the zebrafish embryonic liver. Taken together, these data support an alternative mechanism for hepcidin regulation during zebrafish embryonic development, which is independent of hjv.
Language eng
DOI 10.1371/journal.pone.0014553
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2011, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30062867

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.