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Publication : Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency.

First Author  Shah YM Year  2009
Journal  Cell Metab Volume  9
Issue  2 Pages  152-64
PubMed ID  19147412 Mgi Jnum  J:145975
Mgi Id  MGI:3836383 Doi  10.1016/j.cmet.2008.12.012
Citation  Shah YM, et al. (2009) Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab 9(2):152-64
abstractText  Iron deficiency and iron overload are among the most prevalent nutritional disorders worldwide. Duodenal cytochrome b (DcytB) and divalent metal transporter 1 (DMT1) are regulators of iron absorption. Their expression is increased during high systemic requirements for iron, but the molecular mechanisms that regulate DcytB and DMT1 expression are undefined. Hypoxia-inducible factor (HIF) signaling was induced in the intestine following acute iron deficiency in the duodenum, resulting in activation of DcytB and DMT1 expression and an increase in iron uptake. DcytB and DMT1 were demonstrated as direct HIF-2alpha target genes. Genetic disruption of HIF signaling in the intestine abolished the adaptive induction of iron absorption following iron deficiency, resulting in low systemic iron and hematological defects. These results demonstrate that HIF signaling in the intestine is a critical regulator of systemic iron homeostasis.
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