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The regulation of intestinal iron transport in a rat model of chronic renal failure
Author(s) -
Srai Surjit Kaila,
Sharp Paul A,
Marks Joanne,
Unwin Robert J,
Debnam Edward S
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1011.3
Subject(s) - hepcidin , erythropoietin , erythropoiesis , anemia , endocrinology , medicine , ferroportin , iron deficiency , kidney disease , context (archaeology) , kidney , mononuclear phagocyte system , immunology , biology , paleontology
The hormone erythropoietin (Epo) is produced by the kidney and stimulates erythropoiesis. In chronic renal disease Epo levels are reduced and patients develop anemia, which is treated by administering a combination of iron and recombinant Epo. The mode of action by which Epo improves iron homeostasis is still unclear, but it may involve suppression of the iron regulatory peptide hepcidin. To study the effects of Epo on iron metabolism in chronic renal failure (CRF) we used the well established 5/6 th nephrectomy rat model. CRF animals were treated with human recombinant Epo (100 U/kg body weight) for 5 weeks before experimentation. CRF increased hepatic hepcidin expression and decreased intestinal iron absorption. Following Epo treatment, hepcidin expression significantly decreased and iron absorption was restored to levels found in sham‐operated rats. In intestinal Caco‐2 cells, Epo stimulated iron absorption, suggesting a direct role for Epo in the intestinal handling of iron. In the context of treating anemia in CRF, Epo down‐regulates hepcidin, which in turn permits the release of iron from reticuloendothelial macrophages; in addition Epo stimulates intestinal iron absorption. Together these pathways can normalize iron balance. This work was funded The Roche Foundation for Anemia Research (RoFAR) and Kidney Research UK.