SMAD4 and anemia (phenotype): During conditions of anemia, it has been documented that there is an increase in the expression and release of erythropoietin, leading to a repression of hepcidin expression in the liver, likely by mechanisms such as EPOR-mediated regulation of the transcription factor C/EBPα (13), or indirectly through the suppression of SMAD4 and STAT3 signaling (35).