Hepcidin regulation of iron transport

James F Collins, Marianne Wessling-Resnick, Mitchell D Knutson, James F Collins, Marianne Wessling-Resnick, Mitchell D Knutson

Abstract

The discovery of hepcidin as a key regulator of iron homeostasis has advanced our current knowledge of this field. Liver-derived hepcidin peptide is secreted in response to iron and inflammation and interacts with the iron export protein ferroportin. This review summarizes recent advances discussed at the Symposium. A particular focus is on molecular interactions between hepcidin and ferroportin, the regulation of hepcidin expression by iron and inflammation, and emerging methods to measure serum hepcidin in human populations.

Figures

FIGURE 1
FIGURE 1
Regulation of body iron homeostasis by hepcidin. Hepcidin is secreted primarily by hepatocytes into the circulation, where it functions to inhibit iron absorption in the proximal small intestine and iron release from RE macrophages by binding to its receptor ferroportin and causing its internalization and degradation. Hepcidin gene expression is down-regulated by low tissue oxygen tension and by increased erythropoietic demand and up-regulated by increased body iron stores and infection or inflammation. Up-regulation of hepcidin gene expression during infection and inflammation is in part mediated by IL-6. Signals emanating from these physiological effectors are transduced into the nucleus to regulate hepcidin gene transcription via interaction of the hepcidin gene promoter with several proteins including TfR2, a complex of HFE with TfR1, HJV, SMAD4, and BMP. Hepcidin produced by hepatocytes may also have autocrine and/or paracrine effects on various cell types in the liver, and hepcidin produced by other cell types and tissues may have similar effects. Hepcidin produced by nonhepatic tissues contributes little to circulating hepcidin levels but may have important local effects.

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