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

作者：Worthen Christal A; Enns Caroline A^*

来源：Frontiers in Pharmacology, 2014, 5: 34.

DOI：10.3389/fphar.2014.00034

• transferrin receptor 2
• hereditary hemochromatosis
• iron homeostasis
• hepcidin
• liver

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 Ill hereditary hemochromatosis (HH). With the loss of functionalTfR2, 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 Tf R2 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 transfemn-sensitivity through the B MP-signaling pathway is still not known.

• 出版日期2014-3-6