NDLI: Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease

Content Provider	Journal of Biological Chemistry (JBC)
Author	Das, Nupur Xie, Liwei Ramakrishnan, Sadeesh K. Campbell, Andrew Rivella, Stefano Shah, Yatrik M.
Abstract	Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology.
Related Links	http://www.jbc.org/content/290/39/23523.abstract
Ending Page	23527
Starting Page	23523
Page Count	5
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	39
Volume Number	290
DOI	10.1074/jbc.C115.681643
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2015-09-25
Access Restriction	Open
Subject Keyword	Hypoxia Hypoxia-inducible factor (HIF) Intestinal epithelium Iron Iron metabolism Iron homeostasis Anemia Sickle cell disease HIF-2α Metabolism
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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