Role of duodenal iron transporters and hepcidin in patients with alcoholic liver disease

Journal of Cellular and Molecular Medicine

Marketa Dostalikova-Cimburova²  Kamila Balusikova²  Karolina Kratka³  Jitka Chmelikova²  Vaclav Hejda⁴  Jan Hnanicek¹  Jitka Neubauerova²  Jana Vranova⁵  Jan Kovar² 

[1] Department of Medicine II, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic;Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic;Department of Medicine I, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic;1st Dept. of Medicine, Charles University in Prague, Medical School and Teaching Hospital in Pilsen, Pilsen, Czech Republic;Department of Medical Biophysics and Informatics, Third Faculty of Medicine, Charles University Prague, Prague, Czech Republic

关键词: DMT1;    FPN1;    DCYTB;    HEPH;    TFR1;    HFE;    hepcidin;    alcoholic liver disease;    iron;    gene expression;   

DOI  :  10.1111/jcmm.12310

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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