Open AccessBone Morphogenetic Proteins as Regulators of Iron Metabolism
Author(s) -
Nermi L. Parrow,
Robert E. Fleming
Publication year - 2014
Publication title -
annual review of nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.231
H-Index - 157
eISSN - 1545-4312
pISSN - 0199-9885
DOI - 10.1146/annurev-nutr-071813-105646
Subject(s) - hepcidin , bone morphogenetic protein , smad , microbiology and biotechnology , biology , signal transduction , bone morphogenetic protein 6 , hemochromatosis , endocrinology , hereditary hemochromatosis , bone morphogenetic protein 2 , medicine , bone morphogenetic protein 7 , genetics , immunology , gene , in vitro , inflammation
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-β) superfamily of signaling molecules. In addition to protean roles in embryonic development, germ-line specification, and cellular differentiation, a central role in iron homeostasis has recently been demonstrated for certain BMPs. Specifically, BMP6 serves to relate hepatic iron stores to the hepatocellular expression of the iron-regulatory hormone hepcidin. This regulation occurs via cellular SMAD-signaling molecules and is strongly modulated by the BMP coreceptor hemojuvelin (HJV). Mutations in certain genes influencing signaling to hepcidin via the BMP/SMAD pathway are associated with human disorders of iron metabolism, such as hereditary hemochromatosis and iron-refractory iron-deficiency anemia. Evidence suggests that signals in addition to iron stores influence hepcidin expression via the BMP/SMAD pathway. This review summarizes the details of BMP/SMAD signaling, with a particular focus on its role in iron homeostasis and iron-related diseases.