Iron regulation and erythropoiesis

Curr Opin Hematol. 2008 May;15(3):169-75. doi: 10.1097/MOH.0b013e3282f73335.


Purpose of review: The peptide hormone hepcidin regulates iron metabolism in response to erythropoietic demand, iron stores and inflammation. Major advances have been made in understanding the regulation of hepcidin production, and consequently the availability of iron for erythropoiesis.

Recent findings: It is becoming clear that the bone morphogenetic protein (BMP) pathway plays a major role in setting the baseline hepcidin level and, with the assistance of BMP2/4 and hemochromatosis-related proteins hemojuvelin, HFE and transferrin receptor 2, also regulates hepcidin expression in response to iron. Regulation of hepcidin in anemias has now been linked to increased erythropoietic activity and is likely mediated by factor(s) secreted by erythroid precursors. GDF-15 was identified as a candidate for one of the erythroid factors suppressing hepcidin. Tissue hypoxia may also directly contribute to hepcidin suppression in anemias. Regulation of hepcidin by inflammation may include multiple cytokines and the Toll-like receptors pathways. Although it has not yet been shown that increased hepcidin is indispensible for the development of anemia of inflammation, transgenic overexpression of hepcidin was sufficient to replicate its key features.

Summary: Regulation of hepcidin and iron availability for erythropoiesis has revealed unexpected pathways and much complexity. The renaissance of the study of iron regulation continues to reward researchers with interesting biology and potential therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Cation Transport Proteins / metabolism
  • Erythropoiesis / physiology*
  • Hepcidins
  • Humans
  • Iron / metabolism*
  • Iron Metabolism Disorders / physiopathology*


  • Antimicrobial Cationic Peptides
  • Bone Morphogenetic Proteins
  • Cation Transport Proteins
  • HAMP protein, human
  • Hepcidins
  • metal transporting protein 1
  • Iron