Proceedings of The Physiological Society
Newcastle University (2009) Proc Physiol Soc 16, C12
Direct effects of erythropoietin on iron absorption by human intestinal epithelial cells
B. Chung1, C. Rapisarda1, K. Pourvali1, P. Sharp1
1. Nutritional Sciences Division, King's College London, London, United Kingdom.
Enhanced erythropoiesis in iron deficiency anaemia (IDA) increases the body’s demand for iron. Erythropoietin (Epo) levels are increased in IDA and are thought to act as the main homonal stimulus for red blood cell production. The presumed mode of action of Epo is via inhibition of hepatic hepcidin production which in turn increases iron absorption by intestinal enterocytes and permits iron release from reticuloendothelial macrophages. However, it is also possible that Epo signals the body’s erythroid requirements directly to the enterocytes. To investigate this possibility, we have studied the effects of Epo on intestinal iron absorption in human intestinal Caco-2 cells. Caco-2 cells were grown on Transwell inserts for 17 days prior to experimentation. Epo (1U/ml) was added to the basolateral medium and iron uptake was measured 24 h later. Parallel plates of Epo-treated cells were processed to provide membrane protein and total RNA for the measurement of iron transporter expression. Data were analysed using Student’s unpaired t-test or by one-way ANOVA and Tukey’s post hoc test where appropriate (significant at p<0.05). Iron uptake across the apical membrane (+22%) of Caco-2 cell monolayers and efflux across the basolateral membrane (+171%) were both significantly enhanced in Epo-treated cells (p<0.05). These transport effects were associated with significant increases (p<0.05) in DMT1, ferroportin and hephaestin protein (DMT1, +53%; FPN, +64%; Heph, +58% compared with untreated control cells) and mRNA expression (DMT1, +81%; FPN, +84%; Heph, +183% compared with untreated control cells) in Caco-2 cell exposed to Epo. There was no significant change in Dcytb expression. Our data suggest that Epo can act directly on intestinal epithelial cells to increase dietary iron absorption for subsequent utilisation in the bone marrow. These effects are mediated by Epo receptors, which are expressed on both Caco-2 cells and rat duodenal enterocytes. These data provide a novel insight into the mechanisms by which the body senses and responds to changes in the erythroid requirements for iron.
Where applicable, experiments conform with Society ethical requirements