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 …