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Simvastatin downregulates the expression of hepcidin and erythropoietin in H ep G 2 cells
Author(s) -
Chang ChiaChu,
Chiu PingFang,
Chen HungLin,
Chang TzuLan,
Chang YuJun,
Huang ChingHui
Publication year - 2013
Publication title -
hemodialysis international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.658
H-Index - 47
eISSN - 1542-4758
pISSN - 1492-7535
DOI - 10.1111/j.1542-4758.2012.00716.x
Subject(s) - simvastatin , erythropoietin , erythropoietin receptor , hepcidin , medicine , endocrinology , receptor , downregulation and upregulation , chemistry , inflammation , gene , biochemistry
Statin therapy may improve responsiveness to erythropoietin‐stimulating agents in patients with end‐stage renal disease. Although statins increase hepatic iron uptake and storage capacity in cholestatic rats, the underlying mechanisms are unclear. Therefore, we examined the effects of a statin (simvastatin) on the expression of hepcidin, erythropoietin receptor ( EPOR ) and erythropoietin ( EPO ) in cultured H ep G 2 cells. H ep G 2 cells (6–6.5 × 10 5 cells) were seeded in 6‐cm dishes and incubated overnight. The cells were then treated with 0, 0.5, 1, 3, 5, or 10 μ M simvastatin, and the m RNA expression of hepcidin, EPOR , and EPO was determined. Data were collected from three independent experiments. The c DNA extracted from the cells was used as a template for real‐time polymerase chain reaction, and each sample was tested in duplicate. Significant differences ( P < 0.05) among groups were determined using one‐way analysis of variance with F isher's least significant difference post hoc test. Data were adjusted using B onferroni's method. The relative m RNA expression of hepcidin in H ep G 2 cells treated with 0.5, 1, 3, 5, and 10 μ M simvastatin, relative to the control group, was 0.7273, 0.3303, 0.2418, 0.4131, and 0.4064, respectively. The relative m RNA expression of EPOR was 0.5196, 0.2319, 0.2398, 0.4253, and 0.1245, respectively, while that of EPO was 0.9751, 0.4712, 0.4613, 0.4875, and 0.1654. There was a reverse dose‐dependent effect of simvastatin. These results suggest that statins increase erythropoiesis by targeting hepcidin and iron regulatory pathways, independent of erythropoietin.