Functional and molecular responses of human intestinal Caco-2 cells to iron treatment

Background: Divalent metal transporter 1 (DMT1), HFE, and stimulator of iro n transport (SFT) are transmembrane proteins that have been implicated in t he regulation of iron homeostasis. Objective: The objective of this study was to investigate whether absorptio n and transepithelial movement of iron correlated with gene expression of D MT1, HFE, and SFT in an experimental model of human absorptive enterocytes Design: Caco-2 cells were exposed to iron-supplemented media in either the presence or the absence of serum for 24, 72, and 168 h. At each time point, the uptake and transepithelial movement of iron were examined and gene exp ression of DMT1, HFE, and SFT was measured. Manganese and zinc absorption w as also examined at 168 h. Results: Iron treatment in the presence or absence of serum reduced the upt ake and transepithelial movement of iron by approximate to 50% after 72 and 168 h. No effect was observed at 24 h. The uptake and transepithelial move ment of manganese were similar to those of iron at 168 h, whereas the effec ts on zinc were less pronounced. In the absence of serum, iron treatment wa s associated with a reduction of DMT1 expression by 50% at 72 and 168 h. HF E expression was dependent on serum, but iron treatment did not alter HFE e xpression. SFT expression was not affected by iron. Conclusions: Iron treatment decreased cellular uptake of iron, manganese, a nd zinc, suggesting that these metals may utilize the same apical transport er. The transepithelial movement of iron and manganese, but not of zinc, wa s reduced across iron-treated Caco-2 cells, suggesting that iron and mangan ese are regulated by the same mechanism at the basolateral membrane. The ge ne expression of DMT1, HFE, and SFT did not fully correlate with the functi onal responses of Caco-2 cells. This may have been a result of posttranscri ptional regulation of these genes or regulation of other genes involved in the uptake and transepithelial movement of iron in Caco-2 cells.