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Physiol. Genomics (March 30, 2004). doi:10.1152/physiolgenomics.00211.2003
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Submitted on December 15, 2003
Accepted on March 16, 2004

ADAPTIVE CHANGES OF DUODENAL IRON TRANSPORT PROTEINS IN CELIAC DISEASE

Donatella Barisani1*, Antonina Parafioriti2, Maria Teresa Bardella3, Heinz Zoller4, Dario Conte3, Elisabetta Armiraglio2, Cristina Trovato3, Robert O Koch4, and Gunter Weiss4

1 Department of Experimental and Environmental Medicine and Medical Biotechnology, University of Milano Bicocca, Monza, Milan, Italy
2 Department of Pathology, Istituto Ortopedico Gaetano Pini, Milan, Italy
3 Department of Medical Sciences, IRCCS Ospedale Maggiore, Milan, Italy
4 Department of Internal Medicine, University of Innsbruck, Innsbruck, Austria

* To whom correspondence should be addressed. E-mail: donatella.barisani{at}unimib.it.

Background: Iron deficiency is a manifestation of celiac disease (CD) usually attributed to a decreased absorptive surface, although no data on the regulation of iron transport under these conditions are currently available. Aim: To evaluate Divalent Metal Transporter 1 (DMT1), duodenal cytochrome b (Dcytb), ferroportin 1 (FP1), hephaestin and transferrin receptor 1 (TfR1) expression, as well as iron regulatory protein (IRP) activity in duodenal biopsies from controls, anemics and CD patients. Patients and Methods: Ten subjects with dyspepsia, six with iron-deficiency anemia and 25 with CD were studied. mRNA levels were determined by real-time PCR, protein expression by western blotting or immunohistochemistry and IRP activity by gel shift assay. Results: DMT1, FP1, hephaestin and TfR1 mRNA levels were significantly increased in CD patients with reduced body iron stores as compared to controls, similarly to what was observed in anemics. Protein expression paralleled the mRNAs changes. DMT1 protein expression was localized in differentiated enterocytes at the villi tips in controls, whereas with iron deficiency it was observed throughout the villi. FP1 expression was localized on the basolateral membrane of enterocytes and increased with low iron stores. TfR1 was localized in the crypts in controls, but also in the villi with iron deficiency. These changes were paralleled by IRP activity, which increased in all iron deficient subjects. Conclusions: Duodenal DMT1, FP1, hephaestin and TfR1 expression and IRP activity, thus the iron absorption capacity, are up-regulated in CD patients as a consequence of iron deficiency, whereas the increased enterocyte proliferation observed in CD has no effect on iron uptake regulation.




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