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Activation of Intestinal HIF2α Ameliorates Iron‐Refractory Anemia by Yingying Yu; Yunxing Su; Sisi Yang; Yutong Liu; Zhiting Lin; Nupur K. Das; Qian Wu; Jiahui Zhou; Shumin Sun; Xiaopeng Li; Wuyang Yue; Yatrik M. Shah; Junxia Min; Fudi Wang is a Engineering article available to read on EtoBox.

What is Activation of Intestinal HIF2α Ameliorates Iron‐Refractory Anemia about?

## Abstract In clinics, hepcidin levels are elevated in various anemia‐related conditions, particularly in iron‐refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron‐refractory anemia, the potential effect of hypoxia and pharmacologically‐mimetic drug FG‐4592 (Roxadustat) are evaluated, a hypoxia‐inducible factor (HIF)‐prolyl hydroxylase (PHD) inhibitor, on mouse models of iron‐refractory iron‐deficiency anemia (IRIDA), anemia of inflammation and 5‐fluorouracil‐induced chemotherapy‐related anemia. The potent protective effects of both hypoxia and FG‐4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG‐4592 could stabilize duodenal Hif2α, leading to the activation of __Fpn__ transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin‐activated anemias. Moreover, duodenal __Hif2α__ overexpression fully rescues phenotypes of __Tmprss6__ knockout mice, and __Hif2α__ knockout in the gut significantly delays

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Author

Yingying Yu; Yunxing Su; Sisi Yang; Yutong Liu; Zhiting Lin; Nupur K. Das; Qian Wu; Jiahui Zhou; Shumin Sun; Xiaopeng Li; Wuyang Yue; Yatrik M. Shah; Junxia Min; Fudi Wang

Publisher

John Wiley and Sons Inc.

Published

2024

Language

EN

Field

Engineering (Physical Sciences)