title: Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: n.bergamaschi@smatteo.pv.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Bergamaschi
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: a.disabatino@smatteo.pv.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Sabatino
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: a.pasini@smatteo.pv.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pasini
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: c.ubezio@smatteo.pv.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ubezio
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: filippocostanzo@libero.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Costanzo
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: davide.grat@virgilio.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Grataroli
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: michela_masotti@yahoo.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Masotti
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: c.alvisi@smatteo.pv.it.
authors.forename: Costanza
authors.initials: C
authors.lastname: Alvisi
authors.affiliation: Department of Internal Medicine, University of Pavia Medical School, and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy. Electronic address: g.corazza@smatteo.pv.it.
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000097:blood / Q000235:genetics; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D064451:Hepcidins / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D007501:Iron / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D003573:Cytochrome b Group; C110547:DMRT1 protein; D064451:Hepcidins; D012097:Repressor Proteins; D014157:Transcription Factors; D000098742:Ferroportin; D007501:Iron; D010088:Oxidoreductases; C422926:CYBRD1 protein, human; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: Gene expression; Heme iron; Iron absorption; Stat3