biostudies-literatureYu YNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationNational Institutes of HealthNIH HHSe2307022https://www.ebi.ac.uk/biostudies/studies/S-EPMC10966566biostudies-literatureUnknown11(12)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 FGAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Activation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.PMC109665663220096132200964R01DK09520182030003M642414321711663193005731970689323300472022M712749Wu QWang FLin ZLiu YLi XDas NKMin JSun SShah YMSu YYue WYang SYu YZhou JfalseActivation of Intestinal HIF2α Ameliorates Iron-Refractory Anemia.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 FG2024-01-01T00:00:00Z2024 Mar2025-04-25T21:33:49.445Z2025-04-06T08:48:24.207ZS-EPMC109665663824384710.1002/advs.202307022