title: Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease.
abstract: Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.
authors.affiliation: Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic.
authors.forename: Marketa
authors.initials: M
authors.lastname: Dostalikova-Cimburova
authors.forename: Kamila
authors.initials: K
authors.lastname: Balusikova
authors.forename: Karolina
authors.initials: K
authors.lastname: Kratka
authors.forename: Jitka
authors.initials: J
authors.lastname: Chmelikova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Hejda
authors.forename: Jan
authors.initials: J
authors.lastname: Hnanicek
authors.forename: Jitka
authors.initials: J
authors.lastname: Neubauerova
authors.forename: Jana
authors.initials: J
authors.lastname: Vranova
authors.forename: Jan
authors.initials: J
authors.lastname: Kovar
authors.forename: Jiri
authors.initials: J
authors.lastname: Horak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D064451:Hepcidins / Q000502:physiology*; D006801:Humans; D007501:Iron / Q000097:blood; D008108:Liver Diseases, Alcoholic / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D003573:Cytochrome b Group; D064451:Hepcidins; D007501:Iron; D008565:Membrane Proteins; D010088:Oxidoreductases; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human; C422926:CYBRD1 protein, human
keywords: DCYTB; DMT1; FPN1; HEPH; HFE; TFR1; alcoholic liver disease; gene expression; hepcidin; iron