title: Increased iron loading induces Bmp6 expression in the non-parenchymal cells of the liver independent of the BMP-signaling pathway.
abstract: Bone morphogenetic protein 6 (BMP6) is an essential cytokine for the expression of hepcidin, an iron regulatory hormone secreted predominantly by hepatocytes. Bmp6 expression is upregulated by increased iron-levels in the liver. Both hepatocytes and non-parenchymal liver cells have detectable Bmp6 mRNA. Here we showed that induction of hepcidin expression in hepatocytes by dietary iron is associated with an elevation of Bmp6 mRNA in the non-parenchymal cells of the liver. Consistently, incubation with iron-saturated transferrin induces Bmp6 mRNA expression in isolated hepatic stellate cells, but not in hepatocytes. These observations suggest an important role of the non-parenchymal liver cells in regulating iron-homeostasis by acting as a source of Bmp6.
authors.affiliation: Department of Cell and Developmental Biology, Oregon Health & Science University, Portland, OR, USA. ennsca@ohsu.edu
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Enns
authors.forename: Riffat
authors.initials: R
authors.lastname: Ahmed
authors.forename: Jiaohong
authors.initials: J
authors.lastname: Wang
authors.forename: Akiko
authors.initials: A
authors.lastname: Ueno
authors.forename: Christal
authors.initials: C
authors.lastname: Worthen
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Zhang
mesh_terms: D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
chemical_list: D055418:Bone Morphogenetic Protein 6; D007501:Iron
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