An essential cell-autonomous role for hepcidin in cardiac iron homeostasis
- University of Oxford, United Kingdom
Abstract
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin. We find that while both models maintain normal systemic iron homeostasis, they nonetheless develop fatal contractile and metabolic dysfunction as a consequence of cardiomyocyte iron deficiency. These findings are the first demonstration of a cell-autonomous role for hepcidin in iron homeostasis. They raise the possibility that such function may also be important in other tissues that express both hepcidin and ferroportin, such as the kidney and the brain.
Article and author information
Author details
Samira Lakhal-Littleton
Funding
British Heart Foundation (FS/12/63/29895)
- Samira Lakhal-Littleton
Vifor Pharma (R19874-CN004)
- Magda Wolna
The funders funded the salary and research expenses relating to this work for two of the authors, as described above.
Reviewing Editor
- Richard P Harvey, The Victor Chang Cardiac Research Institute, Australia
Ethics
Animal experimentation: All animal procedures were compliant with and approved under the UK Home Office Animals (Scientific Procedures) Act 1986 (Project Licence number 30/3182). In vivo assessment of cardiac function was carried out under anesthesia (2% Isofluorane) to minimize suffering.
Version history
- Received: July 19, 2016
- Accepted: November 24, 2016
- Accepted Manuscript published: November 29, 2016 (version 1)
- Version of Record published: December 21, 2016 (version 2)
Copyright
© 2016, Lakhal-Littleton et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An essential cell-autonomous role for hepcidin in cardiac iron homeostasis
eLife 5:e19804.
https://doi.org/10.7554/eLife.19804
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