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Linking oxygen, iron and red blood cells

Feb. 6, 2013, 8:00 AM

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The HIF oxygen-sensing pathway plays a central role in regulating new red blood cell production (erythropoiesis) in response to low oxygen (hypoxia), and it may be a good pharmacologic target for treating anemia. HIF (hypoxia-inducible factor) is known to increase the production of erythropoietin (EPO), which stimulates erythropoiesis. However its role in regulating hepcidin, which controls the amount of iron available for new blood cells, is unclear.

Volker Haase, M.D., who holds the Krick-Brooks Chair in Nephrology, Qingdu Liu, Ph.D., and colleagues have now used a genetic approach in mice to dissect the role of HIF in the regulation of hepcidin. They report in the December Journal of Clinical Investigation that HIF suppresses hepcidin (and increases available iron) indirectly, by stimulating EPO-induced erythropoiesis. EPO induction increased levels of growth differentiation factor 15, but EPO itself did not directly regulate hepcidin levels, the researchers showed.

The findings have implications for targeted therapies that aim to exploit the HIF oxygen-sensing pathway for treating anemia and disorders of iron balance.

This research was supported by the Krick-Brooks Chair in Nephrology and by grants from the National Institutes of Health (DK081646, DK080821).

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