Iron is required for multiple cellular functions, including the synthesis of hemoglobin, but a buildup of excess cellular iron can be toxic.
Hepcidin is a circulating molecule produced by the liver that triggers the degradation of iron transporters in the intestine and certain immune cells. In response to rising iron stores, increased hepcidin levels lead to reduced iron absorption from the diet. Iron overload can occur due to inherited mutations in this iron homeostasis pathway, or to disorders that lead to ineffective blood cell development, such as β-thalassemia.
In this issue of the Journal of Clinical Investigation, Shuling Guo, Carla Casu and colleagues at Weill Cornell Medical College in New York increased hepcidin levels by generating molecules that target a negative regulator of hepcidin production called TMPRSS6.
Injection of these molecules improved iron homeostasis and blood cell development in mouse models of iron overload. In the accompanying commentary, Karin Finberg of Duke University how these findings could impact the treatment of patients with β-thalassemia.
TITLE: Reducing TMPRSS6 ameliorates hemochromatosis and beta-thalassemia in mice.