Vitamin C Affects the Expression of Hepcidin and Erythropoietin Receptor in HepG2 Cells

Backgrounds: Hepcidin modulates the de novo absorption of iron from the duodenum and the recycling of iron released from the reticuloendothelial system. In patients with chronic renal failure, administration of higher doses of erythropoietin (EPO) or vitamin C (Vit C) can correct the functional iron deficiency. While EPO-regulated hepcidin expression within hepatocytes has been recently identified, the relation between vitamin C with hepcidin expression is still uncertain. Methods: Hepcidin-producing HepG2 cells (a human liver carcinoma cell line) were cultured with 50- to 100-mu g/mL vitamin C or 0.25- to 1.0-U/mL EPO for 6 hours. Reverse transcription polymerase chain reaction was performed for quantitative measurements of hepcidin, EPO, and EPO receptor (EPOR) expression. Results: EPO and vitamin C inhibited hepcidin expression within HepG2 cells; the EPO effect was dose dependent. EPO downregulated EPOR and vitamin C and upregulated EPOR. However, vitamin C had little effect on the expression of EPO. Conclusions: EPO is capable of downregulating EPOR when it acts early. Vitamin C directly inhibits hepcidin expression within HepG2 cells. Moreover, by enhancing EPOR production, vitamin C may correct the downregulating EPOR from EPO, which has additional effect with EPO in treating anemia. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.