The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body

Christal A. Worthen, Caroline Enns

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Fine-tuning of body iron is required to prevent diseases such as iron-overload and anemia. The putative iron sensor, transferrin receptor 2 (TfR2), is expressed in the liver and mutations in this protein result in the iron-overload disease Type III hereditary hemochromatosis (HH). With the loss of functional TfR2, the liver produces about 2-fold less of the peptide hormone hepcidin, which is responsible for negatively regulating iron uptake from the diet. This reduction in hepcidin expression leads to the slow accumulation of iron in the liver, heart, joints, and pancreas and subsequent cirrhosis, heart disease, arthritis, and diabetes. TfR2 can bind iron-loaded transferrin (Tf) in the bloodstream, and hepatocytes treated with Tf respond with a 2-fold increase in hepcidin expression through stimulation of the bone morphogenetic protein (BMP)-signaling pathway. Loss of functional TfR2 or its binding partner, the original HH protein, results in a loss of this transferrin-sensitivity. While much is known about the trafficking and regulation of TfR2, the mechanism of its transferrin-sensitivity through the BMP-signaling pathway is still not known.

Original languageEnglish (US)
Article numberArticle 034
JournalFrontiers in Pharmacology
Volume5 MAR
DOIs
StatePublished - 2014

Fingerprint

Transferrin Receptors
Transferrin
Hepcidins
Homeostasis
Iron
Liver
Bone Morphogenetic Proteins
Iron Overload
Hemochromatosis
Peptide Hormones
Arthritis
Anemia
Pancreas
Hepatocytes
Heart Diseases
Fibrosis
Joints
Diet
Mutation
Proteins

Keywords

  • Hepcidin
  • Hereditary hemochromatosis
  • Iron homeostasis
  • Liver
  • Transferrin receptor 2

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body. / Worthen, Christal A.; Enns, Caroline.

In: Frontiers in Pharmacology, Vol. 5 MAR, Article 034, 2014.

Research output: Contribution to journalArticle

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