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Am J Physiol Renal Physiol 285: F1050-F1059, 2003. First published July 22, 2003; doi:10.1152/ajprenal.00064.2003
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Altered dietary iron intake is a strong modulator of renal DMT1 expression

Mark Wareing,1 Carole J. Ferguson,1 Mathieu Delannoy,1 Alan G. Cox,2 Raymond F. T. McMahon,3 Roger Green,1 Daniela Riccardi,1 and Craig P. Smith1

1School of Biological Sciences, University of Manchester, Manchester M13 9PT; 2Centre for Analytical Sciences, University of Sheffield, Sheffield S3 7HF; and 3Laboratory Medicine Academic Group, Faculty of Medicine, University of Manchester and Department of Histopathology, Manchester Royal Infirmary, Manchester M13 9WL, United Kingdom

Submitted 14 February 2003 ; accepted in final form 17 July 2003

Divalent metal transporter1 (DMT1; also known as DCT1 or NRAMP2) is an important component of the cellular machinery responsible for dietary iron absorption in the duodenum. DMT1 is also highly expressed in the kidney where it has been suggested to play a role in urinary iron handling. In this study, we determined the effect on renal DMT1 expression of feeding an iron-restricted diet (50 mg/kg) or an iron-enriched diet (5 g/kg) for 4 wk and measured urinary and fecal iron excretion rates. Feeding the low-iron diet caused a reduction in serum iron concentration and fecal iron output rate with an increase in renal DMT1 expression. Feeding an iron-enriched diet had the converse effect. Therefore, DMT1 expression in the kidney is sensitive to dietary iron intake, and the level of expression is inversely related to the dietary iron content. Changes in DMT1 expression occurred intracellularly in the proximal tubule and in the apical membrane and subapical region of the distal convoluted tubule. Increased DMT1 expression was accompanied by a decrease in urinary iron excretion rate and vice versa when DMT1 expression was reduced. Together, these findings suggest that modulation of renal DMT1 expression may influence renal iron excretion rate.

serum iron level; kidney; iron regulatory protein; SLC11A2; NRAMP2


Address for reprint requests and other correspondence: C. P. Smith, School of Biological Sciences, G38, Stopford Bldg., Univ. of Manchester, Oxford Rd., Manchester M13 9PT, UK (E-mail: craig.smith{at}man.ac.uk).




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