Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice

McDonald, Cameron J., Wallace, Daniel F., Ostini, Lesa and Subramaniam, V. Nathan (2014) Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice. American Journal of Physiology: Gastrointestinal and Liver Physiology, 306 2: G132-G139. doi:10.1152/ajpgi.00256.2013


Author McDonald, Cameron J.
Wallace, Daniel F.
Ostini, Lesa
Subramaniam, V. Nathan
Title Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice
Formatted title
Parenteral vs. oral iron: influence on hepcidin signaling pathways through analysis of Hfe/Tfr2-null mice
Journal name American Journal of Physiology: Gastrointestinal and Liver Physiology   Check publisher's open access policy
ISSN 0193-1857
1522-1547
Publication date 2014-01-15
Year available 2013
Sub-type Article (original research)
DOI 10.1152/ajpgi.00256.2013
Open Access Status
Volume 306
Issue 2
Start page G132
End page G139
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Collection year 2014
Language eng
Formatted abstract
Treatment for iron deficiency anemia can involve iron supplementation via dietary or parenteral routes that result in different cellular iron distributions. The effect of the administered iron on the iron regulatory system and hepcidin in the liver has not been well studied. Hepcidin, the liver-expressed central iron-regulatory peptide, is itself regulated through the bone morphogenetic protein (BMP)/SMAD signaling pathway. Specifically, Bmp6 expression is upregulated in response to iron and induces hepcidin through phosphorylation of Smad1/5/8. The hemochromatosis-associated proteins Hfe and transferrin receptor 2 (Tfr2) are known upstream regulators of hepcidin, although their precise roles are still unclear. To investigate the mechanisms of this regulation and the roles of the Hfe and Tfr2, we subjected wild-type, Hfe-/-, Tfr2-/-, and Hfe-/-/Tfr2-/- mice to iron loading via dietary or parenteral routes. Systematic analysis demonstrated that Tfr2 is required for effective upregulation of Bmp6 in response to hepatocyte iron, but not nonparenchymal iron. Hfe is not required for Bmp6 upregulation, regardless of iron localization, but rather, is required for efficient downstream transmission of the regulatory signal. Our results demonstrate that Hfe and Tfr2 play separate roles in the regulatory responses to iron compartmentalized in different cell types and further elucidates the regulatory mechanisms controlling iron homeostasis.
Keyword Bone morphogenetic protein 6
Hepatocyte
Iron metabolism
Kupffer cell
Liver
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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