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. 2023 Sep 7;24(18):13779. doi: 10.3390/ijms241813779

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© 2023 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Model of crosstalk between the erythropoietic system and iron metabolic system. The stimulation of erythropoiesis by ESA is a trigger for crosstalk. When ESA stimulates hematopoiesis (A), serum iron is rapidly consumed and decreases. This triggers a decrease in the expression of hepcidin-25. Iron is then supplied from iron-store cells via FPN. If the supply of iron recovered from senescent red blood cells alone is inadequate, stored iron is consumed. This phenomenon appears to be a shift from FTN iron to RBC iron. In this situation, iron is readily absorbed from the intestinal tract. When erythropoiesis decreases due to the limitation of ESA (B), serum iron increases because of reduced iron consumption in bone marrow, and hepcidin-25 also increases. As a result, the iron supply to blood is suppressed, and unsupplied iron is stored in cells. Iron recovered from senescent red blood cells is also stored. This appears to be a shift from RBC iron to FTN iron. In this situation, iron absorption from the intestinal tract is suppressed. FTN, ferritin; ESA, erythropoiesis-stimulating agent; RBCs, red blood cells.