Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress
2007
Abstract Recent studies have established that erythropoietin (EPO) is a
pleiotropiccytokine. In this study we investigated whether
pleiotropiceffects of EPO may involve regulation of
heme oxygenase(HO)-1, an anti-oxidative stress protein. A stimulatory effect of EPO on HO-1 expression was demonstrated in cultured renal endothelial cells, in which EPO decreased intracellular oxidative stress and provided
cytoprotectionagainst H 2 O 2 . These beneficial effects were partially reversed by a HO-1 inhibitor. We then evaluated whether EPO induces HO-1 and ameliorates renal injury in vivo . Administration of EPO to Dahl salt-sensitive (DS) rats with low salt diet, a model of chronic tubulointerstitial injury, reduced proteinuria, and renal injury including
peritubular capillaries
rarefactionas compared to vehicle-treated DS rats. This renoprotection was associated with up-regulation of HO-1 in the kidney. In conclusion, EPO-induced HO-1 expression is likely to provide
cytoprotectionagainst oxidative stress.
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