Iron attenuates erythropoietin production by decreasing hypoxia-inducible transcription factor 2α concentrations in renal interstitial fibroblasts

Kidney International
Norio SuzukiMasayuki Yamamoto

Abstract

Iron is an essential mineral for oxygen delivery and for a variety of enzymatic activities, but excessive iron results in oxidative cytotoxicity. Because iron is primarily used in red blood cells, defective erythropoiesis caused by loss of the erythroid growth factor erythropoietin (Epo) elevates iron storage levels in serum and tissues. Here, we investigated the effects of iron in a mouse model of Epo-deficiency anemia, in which serum iron concentration was significantly elevated. We found that intraperitoneal injection of iron-dextran caused severe iron deposition in renal interstitial fibroblasts, the site of Epo production. Iron overload induced by either intraperitoneal injection or feeding decreased activity of endogenous Epo gene expression by reducing levels of hypoxia-inducible transcription factor 2α (HIF2α), the major transcriptional activator of the Epo gene. Administration of an iron-deficient diet to the anemic mice reduced serum iron to normal concentration and enhanced the ability of renal Epo production. These results demonstrate that iron overload due to Epo deficiency attenuates endogenous Epo gene expression in the kidneys. Thus, iron suppresses Epo production by reducing HIF2α concentration in renal interst...Continue Reading

Citations

Mar 12, 2019·Current Opinion in Hematology·Cyril Renassia, Carole Peyssonnaux
Jun 20, 2020·Blood·Jeffrey A Gilreath, George M Rodgers
Aug 15, 2020·Antioxidants & Redox Signaling·Tiago L DuarteHal Drakesmith
Nov 5, 2020·International Journal of Molecular Sciences·Deepika WattsBen Wielockx
Feb 12, 2021·Science Advances·Daria BarwinskaUNKNOWN Kidney Precision Medicine Project
Aug 17, 2021·Molecular and Cellular Biology·Anqi ZhangMasayuki Yamamoto

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