Iron Deficiency Induces Epas1 and Iron Transport Gene Expression in the Duodenal Cells Located at the Crypt-Villus Bottom

Abstract

The duodenal epithelium adapting to changes in dietary iron is well appreciated, but the genes and the location of adaptation remain unclear. To examine these issues, RNAs from the crypt-villus bottom (C-pole) and the villus top (V-pole) are isolated form normal, iron deficient and iron-refed rats by gene microarrays. The expression of hypoxia inducible and iron absorptive transcripts and proteins were confirmed by RT-PCR and by Western blot respectively. In iron deficient rats, the duodenum expressed significantly higher transcription factor Arnt and Epas1 (HIf2α), and iron transport related genes such as divalent metal transporter 1 (DMT1), cytochrome b reductase (Cybrd1), ferroportin 1 (FPN1), hephaestin (Heph), heme oxygenase 1 (Hmox1), Slc39a14 (ZIP14) and Slc31a1 (Ctr1) than normal rats. Importantly, all of these genes were precociously expressed in the C-pole. In contrast, the expression of intracellular transporter Slc31a7 (Znt7) was unchanged and Slc25a37 (mitoferrin) was decreased. In iron-refed rats, when hematological criteria were recovering, the Arnt and HIf2α and most iron transport genes retained higher than normal levels, except that Heph, ZIP14 and Ctr1 returned to normal levels. The data demonstrate that dietary iron stimulates the cells at the C-pole to increase nuclear transcription factor and iron transport protein expression that is progresses to cells at the V-poles. The present data support the hypothesis that C-pole cells are responsible for dietary iron adaptation.