25 amino acid peptide that is a controlling agent of iron absorption and iron release from macrophages.

A small peptide hormone produced by the liver.

Central regulator of iron homeostasis.

It is up regulated by circulating iron levels and inflammatory cytokines and down regulated by bone marrow erythroid hyperplasia.

It is the key liver derived negative regulator of iron absorption from the G.I. tract and iron released from body iron stores.

It regulates iron released from cells by binding to its ligand, the key iron export protein ferroportin, which results in internalization and degradation of ferroportin.

Hepcidin binds to ferroportin, which blocks the export of intracellular iron to the blood and leads to reduce levels of serum iron, and transferrin saturation.

Reduced the export of iron results in functional iron deficiency, and decreased erythropoiesis.

Deficiency in hepcidin, a liver peptide, is the central regulator of iron homeostasis and is the key molecular event that can result in iron accumulation.

Its expression is modulated in response to body levels of iron and erythroid iron demand, hypoxia and the presence or absence of inflammation.

Inflammation greatly increases its synthesis, which is important in the pathogenesis of anemia of inflammation.

Hepcidin concentration is suppressed by testosterone, and it suppresses the expression of ferroportin, the membrane protein responsible for the absorption of iron by the enterocyte and the release of iron stored in the monocytes and macrophages of the reticuloendothelial system.

Synthesis is increased predominately but not exclusively because of interleukin-6 which acts to the JA2-STAT 3 pathway to increase the transcription of the hepcidin gene in hepatocytes.

A small peptide produced by the liver, controls the activity of ferroportin by attaching to it and targeting proteins for destruction in the lysozyme.

Mainly secreted by hepatocytes but can be produced by other cell types and organs such as macrophages, adipocytes, heart and kidneys.

Hepcidin synthesis is controlled by feedback from both iron stores and plasma iron levels.

Hepcidin levels fluctuate in response to the body’s need for iron causing less iron absorption with elevated levels, and lower levels of hepcidin associated with more iron absorption.

Bound to Alpha 2 macroglobulin and albumin and can be cleared by the kidney.

Main role is to control surface progression expression of FPN1 by binding to the protein which is internalized and degraded by lysosomes.

FPN1 is the only known iron exporting protein so after its degradation enterocytes, macrophages, and hepatocytes can no longer export iron which is sequestered in these cells.

Hepcidin increased expression decreases plasma iron concentrations and low expression increases concentrations.

When plasma levels of iron are high its synthesis is unregulated.

Impairs the export of iron for macrophages, duodenal enterocytes and hepatocytes by binding to ferroportin, thereby driving internalization and degradation of this key transmembrane iron exporter.

An acute phase reactant that is induced by inflammation.

Chronic inflammatory states such as infections, rheumatologic diseases, cancer and chronic kidney disease decrease urinary clearance of hepcidin and are associated with abnormally high plasma concentrations of hepcidin.

With increased hepcidin levels there is impaired absorption and reutilization of iron, leading to iron restricted anemia of inflammation.

Iron restricted anemia of inflammation is resistant to treatment with supplemental iron and erythropoiesis stimulating agents.

Inhibits iron absorption by inducing internalization of ferroprotin, the iron transporter.

When plasma levels of iron are low the synthesis of hepcidin is down regulated leading to increased ferroportin expression on cell surface and increased dietary iron absorption and iron efflux from the macrophages.

Inhibits cellular iron export.

Synthesized primarily in the liver and is induced by elevated hepatic iron and inflammation.

It restricts the surface expression of the iron exporter ferroportin in macrophages and enterocytes, which are cells that release iron to plasma.

Balance maintained by forces that induce and inhibit hepcidin activity.

Directly correlates between hepatic iron content and its expression.

An acute phase reactant responding to IL-1a and IL-6.

IL-6 stimulates production of hepcidin in the liver, which blocks duodenal iron absorption and down regulates expression of ferroprotein, which prevention of the release of iron from total body stores.

Increased iron stores and inflammation stimuli induce its synthesis, which reduces plasma iron levels, protects tissues from pro-oxidant conditions and restricts availability of iron to pathogens.

Modulates iron homeostasis by inducing internalization and degradation of ferroportin, the cellular iron exporter, expressed by macrophages, hepatocytes and duodenal cells.

It is up regulated by a signaling pathway, that in turn is inhibited by the hepatocyte transmembrane protease TMPRSS6.

Levels reduced below baseline during active erythropoiesis

Hypoxia and anemia are two of the major factors that trigger intestinal iron absorption, and they are independent of iron stores.

Iron refractory iron deficiency anemia (IRIDA) is a genetic process with inappropriately high production of hepcidin, limiting iron absorption and utilization.

Increased serum hepcidin in levels are associated with systemic inflammatory states, such as obesity and may be increased by a factor of more than 10 in patients with sepsis.

Anemia of chronic disease is largely explained by elevated hepcidin production in response to inflammatory cytokines.

Hemochromotosis results from mutations that normally induce hepcidin, and its severity is inversely correlated with hepcidin levels.

In hemachromatosis the hepicidin activating pathway is defective and the severity of iron overload correlates with the degree of hepcidin deficiency.

Thalassemia and other anemias complicated by secondary iron overload, decreased iron production leads to increased iron absorption, exacerbating the iron burden of chronic transfusion treatment.

Iron overload can occur in beta thalassemia, independent of blood transfusions, because hiepcidin is suppressed by ineffective erythropoiesis.

Tmprss6 gene encodes a hepcidin inhibitor, and loss of function mutations in this gene can result in elevated levels of hepcidin and iron deficiency anemia.

Rusfertide is an injectable peptide mimetic of the iron regulatory hormone hepcidin, which restricts the ability of iron for erythropoiesis.

Rusfertide treatments was associated with the mean hematocrit of less than 45% during a 28 week period.

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