A team from Massachusetts, USA, investigated the intestinal expression of genes involved in iron absorption in humans.
Hereditary hemochromatosis (HHC) is one of the most frequent genetic disorders in humans.
In healthy individuals, cells with the highest iron demand, in particular erythroid precursors, tightly regulate absorption of iron in the intestine.
Cloning of intestinal iron transporter proteins has provided new insight into mechanisms and regulation of intestinal iron absorption.
The researchers assessed whether, in humans, the two transporters are regulated in an iron-dependent manner and whether this regulation is disturbed in HHC.
Duodenal biopsy samples were taken from individuals with normal iron levels, iron-deficiency anemia, and iron overload.
Using quantitative PCR, mRNA expression of divalent cation transporter 1 (DCT1), iron-regulated gene 1 (IREG1), and hephaestin were measured in these samples.
| DCT1 and IREG1 mRNA levels are regulated in an iron-dependent manner.
| American Journal of Physiology - Gastrointestinal and Liver Physiology |
In controls, the investigators found inverse relationships between the DCT1 splice form (containing an iron-responsive element [IRE]) and blood hemoglobin, serum transferrin saturation, or ferritin.
Subjects with iron-deficiency anemia showed a significant increase in expression of the spliced form, DCT1(IRE) mRNA.
Similarly, in subjects homozygous for the C282Y HFE mutation, DCT1(IRE) expression levels remained high despite high serum iron saturation.
Furthermore, a significantly increased IREG1 expression was observed.
The team found that hephaestin did not exhibit a similar iron-dependent regulation.
Andreas Rolfs, of the Harvard Medical School, Boston, Massachusetts, said on behalf of the group, "Our data show that expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner. However, hephaestin mRNA is not affected."
"The lack of appropriate downregulation of apical and basolateral iron transporters in duodenum likely leads to excessive iron absorption in persons with HHC," it was concluded.