Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression - PubMed (original) (raw)
doi: 10.1038/ng1777. Epub 2006 Apr 9.
Franklin W Huang, Diedra M Wrighting, Yin Xia, Yisrael Sidis, Tarek A Samad, Jason A Campagna, Raymond T Chung, Alan L Schneyer, Clifford J Woolf, Nancy C Andrews, Herbert Y Lin
Affiliations
- PMID: 16604073
- DOI: 10.1038/ng1777
Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression
Jodie L Babitt et al. Nat Genet. 2006 May.
Abstract
Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression.
Comment in
- Iron metabolism meets signal transduction.
Anderson GJ, Frazer DM. Anderson GJ, et al. Nat Genet. 2006 May;38(5):503-4. doi: 10.1038/ng0506-503. Nat Genet. 2006. PMID: 16642010 No abstract available. - Juvenile hemochromatosis.
Pietrangelo A. Pietrangelo A. J Hepatol. 2006 Dec;45(6):892-4. doi: 10.1016/j.jhep.2006.09.003. Epub 2006 Sep 25. J Hepatol. 2006. PMID: 17034897 No abstract available.
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