Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.
Hemojuvelin (Hjv) is a bone morphogenetic protein (BMP) co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3883712?pdf=render |
| _version_ | 1818523201477541888 |
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| author | Konstantinos Gkouvatsos Carine Fillebeen Alina Daba John Wagner Giada Sebastiani Kostas Pantopoulos |
| author_facet | Konstantinos Gkouvatsos Carine Fillebeen Alina Daba John Wagner Giada Sebastiani Kostas Pantopoulos |
| author_sort | Konstantinos Gkouvatsos |
| collection | DOAJ |
| description | Hemojuvelin (Hjv) is a bone morphogenetic protein (BMP) co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf) was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin. |
| first_indexed | 2024-12-11T05:42:14Z |
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| id | doaj.art-1d2811e1edec4afab6a0e56bd7a93bd8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T05:42:14Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1d2811e1edec4afab6a0e56bd7a93bd82022-12-22T01:19:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8553010.1371/journal.pone.0085530Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.Konstantinos GkouvatsosCarine FillebeenAlina DabaJohn WagnerGiada SebastianiKostas PantopoulosHemojuvelin (Hjv) is a bone morphogenetic protein (BMP) co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf) was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.http://europepmc.org/articles/PMC3883712?pdf=render |
| spellingShingle | Konstantinos Gkouvatsos Carine Fillebeen Alina Daba John Wagner Giada Sebastiani Kostas Pantopoulos Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. PLoS ONE |
| title | Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. |
| title_full | Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. |
| title_fullStr | Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. |
| title_full_unstemmed | Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. |
| title_short | Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels. |
| title_sort | iron dependent regulation of hepcidin in hjv mice evidence that hemojuvelin is dispensable for sensing body iron levels |
| url | http://europepmc.org/articles/PMC3883712?pdf=render |
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