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Hepcidin down‐regulates iron transport across the human intestianal cells
Author(s) -
Han Okhee,
Weaver Veronika
Publication year - 2006
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.20.4.a130-a
Subject(s) - hepcidin , enterocyte , ferroportin , caco 2 , chemistry , epithelial polarity , medicine , endocrinology , inflammation , microbiology and biotechnology , cell , biochemistry , biology , small intestine
Hepcidin is known to control iron homeostasis by regulating intestinal iron absorption and the release of iron from the iron storage sites, such as macrophages and hepatocytes. Hepcidin is synthesized and secreted by the liver in response to iron loading and inflammation/infection. The decrease of hepcidin causes iron overload and the increase of hepcidin results in iron deficiency in humans as well as in animal models. The recent studies suggest the possibility that hepcidin down‐regulates intestinal iron absorption by decreasing the expression of ferroportin‐1, an iron exporter, on the basolateral membrane of the enterocyte. The ferroportin‐1 is expected to function as an iron exporter across the basolateral membrane of the enterocyte. We investigated the effects of hepcidin on iron transport using human intestinal Caco‐2 cells. The fully differentiated Caco‐2 cells grown on microporous membrane inserts were treated with hepcidin (1 μM) in the basolateral compartment overnight. After hepcidin treatments, iron transport across the cell monolayer was assessed using radiolabelled iron ( 55 Fe) and cellular accumulation of 55 Fe was also determined. Hepcidin treatments significantly (p<0.05) decreased iron transport across the enterocyte. In contrast, cellular 55 Fe accumulation was significantly increased in hepcidin‐treated cells. We next examined whether hepcidin treatments change cellular distribution of ferroportin‐1 in the fully differentiated Caco‐2 cells. Our confocal microscope studies show that hepcidin treatments decrease ferroportin‐1 protein expression on the basolateral membrane of intestinal cells. Our results thereby support the possibility that hepcidin may decrease intestinal iron absorption by decreasing levels of the active ferroportin‐1 protein in enterocytes during iron overload and inflammation/infection.