Study On Erythropoietin Involved In Regulation Of Hepcidin In Iron Deficiency Anemia

Iron deficiency is the most common single cause of anemia worldwide, accounting for about half of all anemia cases. At the mean while, the HEPC gene encodes hepcidin as the first mammalian liver-specific antimicrobial peptide and key regulator of iron metabolism, which is controlled by iron stores and the rate of erythropoiesis. These two stimulis has not yet been completely demonstrated. It is also not known whether the erythropoietin-related regulation of hamp expression utilises the bone morphogenetic protein/hemojuvelin pathway.Here, we imitated iron deficiency anemia model by means of iron loss, insufficient of iron absroptionin and hemolysis in order to lucubrate the reason of hepcidin downregulation. In our study, we observed that Epo expression were consistently up-regulated in both liver and kidney of these iron deficiency anemia mice. Recent in vitro studies have shown that EPO mediates hepcidin expression in hepatocytes through EPOR signaling and regulation of C/EBPa, which is a multiple effect on the transcription of a large number of liver-specific genes encoding proteins critical for specific metabolic processes. To analyze precisely the involvement of C/EBPa in the transcriptional control of hepcidin in vivo, we check its production in liver tissue and the results were correspond to hepcidin repression. Subsequently, we confirmed hepcidin suppression by EPO following rhEpo treatment. For further verify the influence of hepcidin expression by BMPs/SMAD pathway, we detect to Bmp6and Idl mRNA levels in the liver of above-mentioned mouse. To our surprised, the change of Bmp6expression was consistent with the change of liver iron concentration, not hepcidin. This result suggests that regulation of EPO to iron deficiency anemia mice is probably not associated with the BMPs/SMAD pathway.This study points out EPO play a critical role in the control of hepcidin in iron deficiency anemia. Our results provide important insights into the effect of EPO as coordinate regulator by other signaling pathways in iron deficiency anemia.