Erythropoietin induces heme oxygenase-1 expression and attenuates oxidative stress.
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.
Katavetin
Pisut
P
Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan.
Inagi
Reiko
R
Miyata
Toshio
T
Shao
Jing
J
Sassa
Ryoji
R
Adler
Stephen
S
Eto
Nobuaki
N
Kato
Hideki
H
Fujita
Toshiro
T
Nangaku
Masaomi
M
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004921:Erythropoietin / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020303:Rats, Inbred Dahl; D016896:Treatment Outcome
D004921:Erythropoietin; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat