Abstract
A classic Girl Scout song says, “Make new friends/but keep the old/One is silver/and
the other gold.” This review focuses on the past decade of discovery in the field
of iron homeostasis, which has identified “new friends” or key modifiers of the critical
systemic iron regulator, hepcidin antimicrobial peptide. The foundation for these
discoveries has been the identification of mutated genes in well-characterized cohorts
of patients with inherited hemochromatosis from across the globe. Transgenic mouse
models of iron overload and iron-restricted anemia have also contributed to understanding
molecular pathophysiology in ways that could never be accomplished in human subjects
alone. The majority of these newly discovered molecules coordinate signaling through
the bone morphogenetic protein pathway of ligands, receptors and coreceptors, intracellular
signaling and transcription. The discovery of these proteins and their interactions
with “old friends,” such as the 1st known hereditary hemochromatosis gene product,
HFE and transferrin receptor, has opened the field of iron homeostasis to include
regulatory networks involving signal transduction pathways, in particular, the mitogen-activated
protein kinase and Smad pathways. These newly discovered partnerships have also made
way for opportunities to develop novel therapeutics for the treatment of iron regulatory
disorders, including hemochromatosis.
Key Indexing Terms
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Article info
Footnotes
Presented as part of the Southern Society for Clinical Investigation’s President’s Symposium at the Southern Regional Meeting, February 22, 2013, New Orleans, Louisiana.
Supported by the Southern Society of Clinical Investigation.
The author has no other conflicts of interest to disclose.
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© 2013 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
