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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2178-2180.
Prepublished online as a Blood First Edition Paper on June 3, 2004; DOI 10.1182/blood-2004-03-0829.


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Inhibition of iron transport across human intestinal epithelial cells by hepcidin

Sachie Yamaji, Paul Sharp, Bala Ramesh, and Surjit Kaila Srai

From the Department of Biochemistry and Molecular Biology, Royal Free and University College London Medical School, London, United Kingdom; and the Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, United Kingdom.

We investigated the effects of the iron regulatory peptide hepcidin on iron transport by the human intestinal epithelial Caco-2 cell line. Caco-2 cells were exposed to hepcidin for 24 hours prior to the measurement of both iron transport and transporter protein and mRNA expression. Incubation with hepcidin significantly decreased apical iron uptake by Caco-2 cells. This was accompanied by a decrease in both the protein and the mRNA expression of the iron-response element containing variant of the divalent metal transporter (DMT1[+IRE]). In contrast, iron efflux and iron-regulated gene1 (IREG1) expression were unaffected by hepcidin. Hepcidin interacts directly with a model intestinal epithelium. The primary effect of this regulatory peptide is to modulate the apical membrane uptake machinery, thereby controlling the amount of iron absorbed from the diet. (Blood. 2004;104:2178-2180)


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