Hepatic transferrin plays a role in systemic iron homeostasis and liver ferroptosis

Although the serum-abundant metal-binding protein transferrin (encoded by the Trf gene) is synthesized primarily in the liver, its function in the liver is largely unknown. Here, we generated hepatocyte-specific Trf knockout mice (Trf-LKO), which are viable and fertile but have impaired erythropoiesis and altered iron metabolism. Moreover, feeding Trf-LKO mice a high-iron diet increased their susceptibility to developing ferroptosis-induced liver fibrosis. Importantly, we found that treating Trf-LKO mice with the ferroptosis inhibitor ferrostatin-1 potently rescued liver fibrosis induced by either high dietary iron or carbon tetrachloride (CCl4) injections. In addition, deleting hepatic Slc39a14 expression in…

• NN
  National Natural Science Foundation of China

  Awards: 31701034, 2018YFA0507802, 31701035, 31930057, 2018YFA0507801, 31530034, 31570791, 91542205
• CP
  China Postdoctoral Science Foundation

  Awards: 2018YFA0507801, 2019M650139, 31930057, 2018YFA0507802
• ZU
  Zhejiang University
• NK
  National Key Research and Development Program of China

  Awards: 2018YFA0507801, 2018YFA0507802, 31930057