title: Skeletal muscle hemojuvelin is dispensable for systemic iron homeostasis.
abstract: Hepcidin, a hormone produced mainly by the liver, has been shown to inhibit both intestinal iron absorption and iron release from macrophages. Hemojuvelin, a glycophosphatidyl inositol-linked membrane protein, acts as a bone morphogenetic protein coreceptor to activate hepcidin expression through a SMAD signaling pathway in hepatocytes. In the present study, we show in mice that loss of hemojuvelin specifically in the liver leads to decreased liver hepcidin production and increased tissue and serum iron levels. Although it does not have any known function outside of the liver, hemojuvelin is expressed at very high levels in cardiac and skeletal muscle. To explore possible roles for hemojuvelin in skeletal muscle, we analyzed conditional knockout mice that lack muscle hemojuvelin. The mutant animals had no apparent phenotypic abnormalities. We found that systemic iron homeostasis and liver hepcidin expression were not affected by loss of hemojuvelin in skeletal muscle regardless of dietary iron content. We conclude that, in spite of its expression pattern, hemojuvelin is primarily important in the liver.
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Chen
authors.forename: Franklin W
authors.initials: FW
authors.lastname: Huang
authors.forename: Tomasa Barrientos
authors.initials: TB
authors.lastname: de Renshaw
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Andrews
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D008565:Membrane Proteins; D009124:Muscle Proteins; D051785:Smad Proteins; D007501:Iron