Erythroferrone is a hormone secreted by the bone marrow erythroblasts and plays a
pivotal role in erythropoiesis. Describe the role of erythroferrone as erythroid
regulator of hepcidin and iron metabolism.
Iron is an essential component of hemoglobin for the transport of oxygen to tissues. The
majority of iron is obtained from dietary sources and the recycling of senescent erythrocytes.
Insufficient iron availability affects the erythropoiesis process (Han et al., 2001). Iron
regulatory mechanisms are required to control iron hemostasis and ensure adequate iron
supply (Knutson et al., 2005). Ferroportin is known as a cellular iron exporter protein and
hepcidin receptor; it exports stored iron from iron-storing cells into plasma. Thus, balancing
iron absorption and recycling (Donovan et al., 2005) (Knutson et al., 2005). Hepcidin is a
regulatory hormone produced from hepatocytes and plays a role in controlling both iron
hemostasis and ferroportin (Nemeth et al., 2004) (Zumerle et al., 2014). Moreover, hepcidin
inhibits iron absorption and recycling by regulating iron flows into plasma, absorption of
dietary iron from enterocytes in the intestine, recycling of iron by macrophages, and
mobilization of stored iron from hepatocytes (Nemeth et al., 2005) (Ganz and Nemeth, 2012).
Hepcidin reduces ferroportin activity by two mechanisms: blocking ferroportin from iron
transport, and binding to ferroportin, which results in inducing conformational changes that
cause degradation. Decreased ferroportin activity leads to decreased iron absorption, iron
retention in exporting cells, and iron flow into plasma (Aschemeyer et al., 2018). Production
of hepcidin depends on changes related to iron, such as iron concentration, stores, and iron-
restricted erythropoiesis. Furthermore, increases in hepcidin correlate with high serum iron
concentration and hepatocytes iron stores while decreases correlate with iron deficiency
condition such as anemias (Ramos et al., 2011). Ferroportin remains stable on the surface of
iron-storing cells; hepatocytes, enterocytes, and macrophages and increases releasing of iron
into the plasma from dietary and stored sources in the absence of hepcidin (Nemeth et al.,
2004). The erythroid regulators help in iron delivery to the erythroblast by reducing hepcidin
concentrations in the blood. In the Kautz et al. study, erythroferrone (ERFE) was discovered
as a hormone produced from marrow erythroblasts in response to erythropoietin (EPO)
(Kautz et al., 2014). EPO is a hormone produced by the kidney to promote red blood cell
production and has a suppressive effect on hepcidin (Pak et al., 2006). ERFE is an essential
erythroid regulator that suppresses hepcidin production from hepatocytes after erythropoietic
stimulation (Kautz et al., 2014). The suppression mechanism of ERFE is by binding and
sequestering with hepcidin's transcriptional regulatory pathway, bone morphogenetic protein
(BMP) family-SMAD signaling in the liver (Wang et al., 2017) (Castro-Mollo et al., 2021).
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pivotal role in erythropoiesis. Describe the role of erythroferrone as erythroid
regulator of hepcidin and iron metabolism.
Iron is an essential component of hemoglobin for the transport of oxygen to tissues. The
majority of iron is obtained from dietary sources and the recycling of senescent erythrocytes.
Insufficient iron availability affects the erythropoiesis process (Han et al., 2001). Iron
regulatory mechanisms are required to control iron hemostasis and ensure adequate iron
supply (Knutson et al., 2005). Ferroportin is known as a cellular iron exporter protein and
hepcidin receptor; it exports stored iron from iron-storing cells into plasma. Thus, balancing
iron absorption and recycling (Donovan et al., 2005) (Knutson et al., 2005). Hepcidin is a
regulatory hormone produced from hepatocytes and plays a role in controlling both iron
hemostasis and ferroportin (Nemeth et al., 2004) (Zumerle et al., 2014). Moreover, hepcidin
inhibits iron absorption and recycling by regulating iron flows into plasma, absorption of
dietary iron from enterocytes in the intestine, recycling of iron by macrophages, and
mobilization of stored iron from hepatocytes (Nemeth et al., 2005) (Ganz and Nemeth, 2012).
Hepcidin reduces ferroportin activity by two mechanisms: blocking ferroportin from iron
transport, and binding to ferroportin, which results in inducing conformational changes that
cause degradation. Decreased ferroportin activity leads to decreased iron absorption, iron
retention in exporting cells, and iron flow into plasma (Aschemeyer et al., 2018). Production
of hepcidin depends on changes related to iron, such as iron concentration, stores, and iron-
restricted erythropoiesis. Furthermore, increases in hepcidin correlate with high serum iron
concentration and hepatocytes iron stores while decreases correlate with iron deficiency
condition such as anemias (Ramos et al., 2011). Ferroportin remains stable on the surface of
iron-storing cells; hepatocytes, enterocytes, and macrophages and increases releasing of iron
into the plasma from dietary and stored sources in the absence of hepcidin (Nemeth et al.,
2004). The erythroid regulators help in iron delivery to the erythroblast by reducing hepcidin
concentrations in the blood. In the Kautz et al. study, erythroferrone (ERFE) was discovered
as a hormone produced from marrow erythroblasts in response to erythropoietin (EPO)
(Kautz et al., 2014). EPO is a hormone produced by the kidney to promote red blood cell
production and has a suppressive effect on hepcidin (Pak et al., 2006). ERFE is an essential
erythroid regulator that suppresses hepcidin production from hepatocytes after erythropoietic
stimulation (Kautz et al., 2014). The suppression mechanism of ERFE is by binding and
sequestering with hepcidin's transcriptional regulatory pathway, bone morphogenetic protein
(BMP) family-SMAD signaling in the liver (Wang et al., 2017) (Castro-Mollo et al., 2021).
1
