Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency
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 mechani...
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| Veröffentlicht in: | Cell metabolism 2009-02, Vol.9 (2), p.152-164 |
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| creator | Shah, Yatrik M. Matsubara, Tsutomu Ito, Shinji Yim, Sun-Hee Gonzalez, Frank J. |
| description | 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-2α 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. |
| doi_str_mv | 10.1016/j.cmet.2008.12.012 |
| format | Article |
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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-2α 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.</description><identifier>ISSN: 1550-4131</identifier><identifier>EISSN: 1932-7420</identifier><identifier>DOI: 10.1016/j.cmet.2008.12.012</identifier><identifier>PMID: 19147412</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator - metabolism ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Cation Transport Proteins - metabolism ; Cytochrome b Group - metabolism ; Duodenum - metabolism ; Hypoxia-Inducible Factor 1 - metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Iron - deficiency ; Iron - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oxidoreductases - metabolism ; Signal Transduction</subject><ispartof>Cell metabolism, 2009-02, Vol.9 (2), p.152-164</ispartof><rights>2009 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c519t-bc48bce4cd685cab7b5789390e9e6ef9ab85d4d057e370d9c8f9c537585479173</citedby><cites>FETCH-LOGICAL-c519t-bc48bce4cd685cab7b5789390e9e6ef9ab85d4d057e370d9c8f9c537585479173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1550413108004191$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19147412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Yatrik M.</creatorcontrib><creatorcontrib>Matsubara, Tsutomu</creatorcontrib><creatorcontrib>Ito, Shinji</creatorcontrib><creatorcontrib>Yim, Sun-Hee</creatorcontrib><creatorcontrib>Gonzalez, Frank J.</creatorcontrib><title>Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency</title><title>Cell metabolism</title><addtitle>Cell Metab</addtitle><description>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-2α 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. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Aryl Hydrocarbon Receptor Nuclear Translocator - metabolism Basic Helix-Loop-Helix Transcription Factors - metabolism Cation Transport Proteins - metabolism Cytochrome b Group - metabolism Duodenum - metabolism Hypoxia-Inducible Factor 1 - metabolism Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Iron - deficiency Iron - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Oxidoreductases - metabolism Signal Transduction |
| title | Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency |
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