title: Hepatic expression of hemochromatosis genes in two mouse strains after phlebotomy and iron overload.
abstract: OBJECTIVE
  Iron homeostasis is tightly regulated in mammals according to the needs of erythropoiesis and the iron stores present. This regulation is disrupted in hereditary hemochromatosis (HH), a genetic disorder characterized by increased intestinal iron absorption, leading to iron overload. The genes coding for HFE, transferrin receptor 2 (TFR2), ferroportin (SLC40A1 or FPN1), hepcidin (HEPC) and hemojuvelin (HJV or RGMC) are responsible for different types of genetic iron overload. All these genes are highly expressed in the liver and their protein products are likely components of a single hepcidin-related pathway. In order to gain insights into the molecular relationship among the HH proteins we evaluated the hepatic expression of HH genes in conditions of iron restriction or overload.
  
  
  METHODS
  Data were obtained after phlebotomy, to activate the erythroid regulators and following parenteral iron dextran loading, to activate the store regulators, in two mice strains (C57BL/6 and DBA/2). HH genes and proteins expression were analyzed by quantitative real time polymerase chain reaction and by Western blotting, respectively.
  
  
  RESULTS
  Hepc RNA was reduced after phlebotomy and increased in iron overload. A statistically significant reduction of hepatic Fpn1 RNA expression was observed after phlebotomy; this effect was more evident in the DBA/2 strain. Fpn1 increased in C57BL/6 mice, but not in the DBA/2 ones in parenteral iron loading. Fpn1 protein did not change substantially in either condition. Hfe, Rgmc and Tfr2 expression was not influenced by phlebotomy. In parenteral iron overload, Tfr2 gene and protein expression decreased concomitant to the increase in Hepc, while Hfe RNA remained constant.
  
  
  CONCLUSIONS
  Our results indicate that regulation of hepatic Fpn1 differs from that reported for duodenal Fpn1. Furthermore, taken the differences in gene expression in dietary overload (increased Hfe but not Tfr2), distinct roles are suggested for Hfe and Tfr2 in Hepc activation.
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi, Orbassano, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bondi
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Filomena
authors.initials: F
authors.lastname: Daraio
authors.forename: Paolo
authors.initials: P
authors.lastname: Porporato
authors.forename: Enrico
authors.initials: E
authors.lastname: Gramaglia
authors.forename: Sonia
authors.initials: S
authors.lastname: Carturan
authors.forename: Enrico
authors.initials: E
authors.lastname: Gottardi
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.forename: Antonella
authors.initials: A
authors.lastname: Roetto
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018962:Phlebotomy; D013045:Species Specificity; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D000098742:Ferroportin