Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin

Gaetano Bergamaschi, Antonio Di Sabatino, Alessandra Pasini, Cristina Ubezio, Filippo Costanzo, Davide Grataroli, Michela Masotti, Costanza Alvisi, Gino R. Corazza

Research output: Contribution to journalArticle

Abstract

Background & aims: Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin. Methods: The transcriptional response of human duodenal mucosa to hepcidin was investigated using organ cultures of duodenal biopsies perendoscopically collected from healthy controls. Biopsies were cultured for 4 h with or without hepcidin-25 and were then assayed for the expression of iron-related genes. Results: In samples that had not been exposed to hepcidin, correlations were found between the expression of genes involved in iron absorption: . DMT1, . Fpn1, . Dcytb and . HCP1. In . ex vivo experiments hepcidin down-regulated mRNA levels of the iron transporters . Fpn1, and . DMT1, of the ferric reductase . Dcytb, of the ferroxidase . hephaestin, and of the putative heme carrier protein . HCP1. Conclusions: Through the reported transcriptional changes hepcidin can modulate several steps of the iron absorption process, including the reduction of dietary iron by Dcytb, its uptake by enterocytes through DMT1, the mucosal uptake of heme iron by HCP1, and enterocyte iron release to plasma by Fpn1 in conjunction with hephaestin.

Original languageEnglish
JournalClinical Nutrition
DOIs
Publication statusAccepted/In press - Aug 7 2015

Keywords

  • Gene expression
  • Heme iron
  • Iron absorption
  • Stat3

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Critical Care and Intensive Care Medicine

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