Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress

Pisut Katavetin, Reiko Inagi, Toshio Miyata, Jing Shao, Ryoji Sassa, Stephen Adler, Nobuaki Eto, Hideki Kato, Toshiro Fujita, Masaomi Nangaku

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83 Citations (Scopus)


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 H2O2. 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.

Original languageEnglish
Pages (from-to)928-934
Number of pages7
JournalBiochemical and Biophysical Research Communications
Issue number4
Publication statusPublished - 2007 Aug 10


  • Chronic tubulointerstitial injury
  • Intracellular reactive oxygen species
  • Renal endothelial cells
  • Renoprotection


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