BMP signaling modulates hepcidin expression in zebrafish embryos independent of hemojuvelin
| Autor: | Victoria J. Lattanzi, Sarah A. Faasse, Lea M. Vedder, Yann Gibert, Paula G. Fraenkel, Aileen W. Zhen, Frédéric Brunet, Jodie L. Babitt, Matthias Hammerschmidt, Herbert Y. Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Embryo
Nonmammalian animal structures Morpholino Notochord Bone Morphogenetic Protein 2 lcsh:Medicine GPI-Linked Proteins Bone morphogenetic protein 03 medical and health sciences 0302 clinical medicine Hepcidins Hepcidin Animals Humans Hematology/Disorders of Red Cell Metabolism Hemochromatosis Protein Promoter Regions Genetic lcsh:Science Zebrafish Furin 030304 developmental biology Hemojuvelin 0303 health sciences Gene knockdown Multidisciplinary biology Serine Endopeptidases fungi lcsh:R Zebrafish Proteins biology.organism_classification Molecular biology Anti-Bacterial Agents Liver Somites 030220 oncology & carcinogenesis Bone Morphogenetic Proteins embryonic structures Trans-Activators biology.protein Hematology/Anemias lcsh:Q Hemochromatosis Developmental Biology/Developmental Evolution Signal transduction Antimicrobial Cationic Peptides Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 6, Iss 1, p e14553 (2011) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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