NDLI: Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine

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Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine

Content Provider	PubMed Central
Author	Yeh, Kwo-yih Yeh, Mary Polk, Paula Glass, Jonathan
Copyright Year	2011
Abstract	The divalent metal transporter (DMT1, Slc11a2) is an important molecule for intestinal iron absorption. In the Belgrade (b/b) rat, the DMT1 G185R mutation markedly decreases intestinal iron absorption. We used b/b rats as a model to examine the genes that could be compensatory for decreased iron absorption. When tissue hypoxia was assayed by detecting pimonidazole HCl adducts, the b/b liver and intestine exhibited more adducts than the +/+ rats, suggesting that hypoxia might signal altered gene expression. Total RNA in the crypt-villus bottom (C-pole) and villus top (V-pole) of +/+, b/b, and iron-fed b/b rats was isolated for gene array analyses. In addition, hepatic hepcidin and intestinal hypoxia-inducible factor-α (Hifα) expression were examined. The results showed that expression of hepatic hepcidin was significantly decreased and intestinal Hif2α was significantly increased in b/b and iron-fed b/b than +/+ rats. In b/b rats, the expression of Tfrc mRNA in the C-pole and of DMT1, Dcytb, FPN1, Heph, Hmox1, and ZIP14 mRNAs in the V-pole were markedly enhanced with increases occurring even in the C-pole. After iron feeding, the increased expression found in b/b rats persisted, except for Heph and ZIP14, which returned to normal levels. Thus in b/b rats depressed liver hepcidin production and activated intestinal Hif2α starting at the C-pole resulted in increasing expression of iron transport genes, including DMT1 G185R, in an attempt to compensate for the anemia in Belgrade rats.
Related Links	http://dx.doi.org/10.1152/ajpgi.00538.2010
Starting Page	82
File Format	PDF
ISSN	01931857
e-ISSN	15221547
Journal	American Journal of Physiology - Gastrointestinal and Liver Physiology
Issue Number	1
Volume Number	301
Language	English
Publisher	American Physiological Society
Publisher Date	2011-07-01
Access Restriction	Open
Rights Holder	American Physiological Society
Subject Keyword	Hepatology Gastroenterology Physiology (medical) Physiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

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