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

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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
Pages (from-to)1427-1433
Number of pages7
JournalClinical Nutrition
Volume36
Issue number5
DOIs
Publication statusPublished - Oct 1 2017

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Hepcidins
Iron
Gene Expression
Enterocytes
Dietary Iron
Hemeproteins
Biopsy
Ceruloplasmin
Organ Culture Techniques
Plasma Cells
Heme
Hepatocytes
Carrier Proteins

Keywords

  • Gene expression
  • Heme iron
  • Iron absorption
  • Stat3

Cite this

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title = "Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin",
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.",
keywords = "Gene expression, Heme iron, Iron absorption, Stat3",
author = "G. Bergamaschi and Sabatino, {A. Di} and A. Pasini and C. Ubezio and F. Costanzo and D. Grataroli and M. Masotti and C. Alvisi and Corazza, {G. R.}",
note = "LR: 20170822; CI: Copyright (c) 2016; JID: 8309603; OTO: NOTNLM; 2015/08/07 00:00 [received]; 2016/06/16 00:00 [revised]; 2016/09/23 00:00 [accepted]; 2016/10/13 06:00 [pubmed]; 2016/10/13 06:00 [medline]; 2016/10/13 06:00 [entrez]; ppublish",
year = "2017",
month = "10",
day = "1",
doi = "S0261-5614(16)31261-4 [pii]",
language = "English",
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pages = "1427--1433",
journal = "Clinical Nutrition",
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TY - JOUR

T1 - Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin

AU - Bergamaschi, G.

AU - Sabatino, A. Di

AU - Pasini, A.

AU - Ubezio, C.

AU - Costanzo, F.

AU - Grataroli, D.

AU - Masotti, M.

AU - Alvisi, C.

AU - Corazza, G. R.

N1 - LR: 20170822; CI: Copyright (c) 2016; JID: 8309603; OTO: NOTNLM; 2015/08/07 00:00 [received]; 2016/06/16 00:00 [revised]; 2016/09/23 00:00 [accepted]; 2016/10/13 06:00 [pubmed]; 2016/10/13 06:00 [medline]; 2016/10/13 06:00 [entrez]; ppublish

PY - 2017/10/1

Y1 - 2017/10/1

N2 - 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.

AB - 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.

KW - Gene expression

KW - Heme iron

KW - Iron absorption

KW - Stat3

U2 - S0261-5614(16)31261-4 [pii]

DO - S0261-5614(16)31261-4 [pii]

M3 - Article

VL - 36

SP - 1427

EP - 1433

JO - Clinical Nutrition

JF - Clinical Nutrition

SN - 0261-5614

IS - 5

ER -