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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3940-3944.
Prepublished online as a Blood First Edition Paper on January 29, 2004; DOI 10.1182/blood-2003-03-0953.


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Submitted March 27, 2003
Accepted January 21, 2004

Effect of hepcidin on intestinal iron absorption in mice

Abas H Laftah, Bala Ramesh, Robert J Simpson, Nita Solanky, Seiamak Bahram, Klaus Schumann, Edward S Debnam, and Surjit K Srai*

Life Sciences, King's College London, London, United Kingdom
Biochemistry & Molecular Biology, Royal Free & University College Medical School, London, United Kingdom
Centre de Recherche d'Immunologie et d'He'matologie, INSERM-CreS, Strasbourg, Cedex, France
Walther-Straub-institute fur Pharmakologie und Toxicologie, Ludwig-Maxmilians-Universitat, Munchen, Germany
Physiology, Royal Free & University College School of Medicine, London, United Kingdom

* Corresponding author; email: ksrai{at}rfc.ucl.ac.uk.

The effect of the putative iron regulatory peptide hepcidin on iron absorption was investigated in mice. Hepcidin peptide was synthesised, injected into mice for up to 3 days and in vivo iron absorption measured with tied-off segments of duodenum. Liver hepcidin expression was measured by RT-PCR. Hepcidin significantly reduced mucosal iron uptake and transfer to the carcass at doses of at least 10µg/mouse/day, the reduction in transfer to the carcass being proportional to the reduction in iron uptake. Synthetic hepcidin injections down-regulated endogenous liver hepcidin expression excluding the possibility that synthetic hepcidin was functioning by a secondary induction of endogenous hepcidin. The effect of hepcidin was significant at least 24h after injection of hepcidin. Liver iron stores and hemoglobin levels were unaffected by hepcidin injection. Similar effects of hepcidin on iron absorption were seen in iron deficient and Hfe KO mice. Hepcidin inhibited the uptake step of duodenal iron absorption but did not affect the proportion of iron transferred to the circulation. The effect was independent of iron status of mice and did not require Hfe gene product. The data support a key role for hepcidin in the regulation of intestinal iron uptake.


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