LSECs produce BMP2 and BMP6, possibly related to iron-loaded transferrin and ferritin. The BMPs regulate hepatocellular hepcidin expression in a paracrine fashion via BMP type II and type I receptors. Which specific receptor subtypes participate might be influenced by the BMP subtype; likewise, the ability of HJV to serve as a coreceptor might also depend on the BMP subtype. In both instances, type I receptor activation results in the recruitment and phosphorylation of SMAD1/5/8. Phosphorylated SMAD1/5/8 then forms a complex with the common SMAD, SMAD4, which translocates to the nucleus, where it binds the hepcidin promoter to induce expression. The roles of TFR2 and HFE are not completely defined, but may respond to iron-loaded transferrin to influence signaling through the SMAD (and possibly MAPK) pathways. Fe2-Tf, diferric transferrin.