title: Hepcidin expression in the liver of rats fed a magnesium-deficient diet.
abstract: Mg deficiency accelerates Fe accumulation in the liver, which may induce various metabolic disturbances. In the present study, we examined the gene expression of Hepcidin, a peptide hormone produced in the liver to regulate intestinal Fe absorption negatively, in Mg-deficient rats. Although liver Fe concentration was significantly higher in rats fed an Mg-deficient diet for 4 weeks than in rats fed a control diet, Hepcidin expression in the liver was comparable between the dietary groups. Previous studies revealed that Fe overload up-regulated Hepcidin expression through transcriptional activation by Fe-induced bone morphogenetic protein (Bmp) 6, a growth/differentiation factor belonging to the transforming growth factor-β family, in the liver. Mg deficiency up-regulated the expression of Bmp6 but did not affect the expression of inhibition of DNA binding 1, a sensitive Bmp-responsive gene. In addition, the expression of Bmp receptors such as activin receptor-like kinase 2 (Alk2), activin receptor type IIA (Actr2a), activin receptor type IIB (Actr2b) and Bmp type II receptor (Bmpr2) was lower in the liver of Mg-deficient rats than in that of control rats. The present study indicates that accumulation of hepatic Fe by Mg deficiency is a stimulant inducing Bmp6 expression but not Hepcidin expression by blunting Bmp signalling possibly resulting from down-regulation of the receptor expression. Unresponsive Hepcidin expression may have a role in Mg deficiency-induced changes related to increased liver Fe.
authors: Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwakecho, Kyoto 606-8502, Japan.
authors: Natsumi
authors: N
authors: Ishizaki
authors: Megumi
authors: M
authors: Kotani
authors: Masayuki
authors: M
authors: Funaba
authors: Tohru
authors: T
authors: Matsui
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D001483:Base Sequence; D055418:Bone Morphogenetic Protein 6 / Q000235:genetics; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008274:Magnesium / Q000097:blood; D008275:Magnesium Deficiency / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000235:genetics; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C525818:Bmp6 protein, rat; D055418:Bone Morphogenetic Protein 6; D017931:DNA Primers; D058851:GPI-Linked Proteins; C484232:HFE protein, rat; C578703:Hamp protein, rat; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; C513726:Hjv protein, rat; C497454:ID1 protein, rat; D051798:Inhibitor of Differentiation Protein 1; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C548977:Tfr2 protein, rat; C545564:Tfrc protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D007501:Iron; D052004:Bone Morphogenetic Protein Receptors; D008274:Magnesium