Iron Regulation of Hepcidin Despite Attenuated Smad1,5,8 Signaling in Mice Without Transferrin Receptor 2 or Hfe

These observations show that Tfr2 and Hfe are each required for normal signaling of iron status to hepcidin via the Bmp6/Smad1,5,8 pathway. Mice with combined loss of Hfe and Tfr2 up-regulate hepcidin in response to dietary iron loading without increases in liver Bmp6 messenger RNA or steady-state P-Smad1,5,8 levels.