Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress |
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Authors: | Katavetin Pisut Inagi Reiko Miyata Toshio Shao Jing Sassa Ryoji Adler Stephen Eto Nobuaki Kato Hideki Fujita Toshiro Nangaku Masaomi |
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Institution: | Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan. |
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Abstract: | Recent studies have established that erythropoietin (EPO) is a pleiotropic cytokine. In this study we investigated whether pleiotropic effects 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 cytoprotection against 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 rarefaction as 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 cytoprotection against oxidative stress. |
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Keywords: | Renal endothelial cells Intracellular reactive oxygen species Chronic tubulointerstitial injury Renoprotection |
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