title: Iron-dependent regulation of hepcidin in Hjv-/- mice: evidence that hemojuvelin is dispensable for sensing body iron levels.
abstract: Hemojuvelin (Hjv) is a bone morphogenetic protein (BMP) co-receptor involved in the control of systemic iron homeostasis. Functional inactivation of Hjv leads to severe iron overload in humans and mice due to marked suppression of the iron-regulatory hormone hepcidin. To investigate the role of Hjv in body iron sensing, Hjv-/- mice and isogenic wild type controls were placed on a moderately low, a standard or a high iron diet for four weeks. Hjv-/- mice developed systemic iron overload under all regimens. Transferrin (Tf) was highly saturated regardless of the dietary iron content, while liver iron deposition was proportional to it. Hepcidin mRNA expression responded to fluctuations in dietary iron intake, despite the absence of Hjv. Nevertheless, iron-dependent upregulation of hepcidin was more than an order of magnitude lower compared to that seen in wild type controls. Likewise, iron signaling via the BMP/Smad pathway was preserved but substantially attenuated. These findings suggest that Hjv is not required for sensing of body iron levels and merely functions as an enhancer for iron signaling to hepcidin.
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Gkouvatsos
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Carine
authors.initials: C
authors.lastname: Fillebeen
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Alina
authors.initials: A
authors.lastname: Daba
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Wagner
authors.affiliation: Division of Gastroenterology, Royal Victoria Hospital, McGill University Health Center, Montreal, Quebec, Canada ; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Giada
authors.initials: G
authors.lastname: Sebastiani
authors.affiliation: Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada ; Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Kostas
authors.initials: K
authors.lastname: Pantopoulos
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D005838:Genotype; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D007501:Iron / Q000097:blood / Q000378:metabolism*; D019266:Iron, Dietary / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000473:pathology
chemical_list: D055418:Bone Morphogenetic Protein 6; D058851:GPI-Linked Proteins; C504414:HJV protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D019266:Iron, Dietary; D008565:Membrane Proteins; D051785:Smad Proteins; D007501:Iron