Carbamylated erythropoietin protects the kidneys from ischemia-reperfusion injury without stimulating erythropoiesis.
Several studies have shown that erythropoietin (EPO) can protect the kidneys from ischemia-reperfusion injury and can raise the hemoglobin (Hb) concentration. Recently, the EPO molecule modified by carbamylation (CEPO) has been identified and was demonstrated to be able to protect several organs without increasing the Hb concentration. We hypothesized that treatment with CEPO would protect the kidneys from tubular apoptosis and inhibit subsequent tubulointerstitial injury without erythropoiesis. The therapeutic effect of CEPO was evaluated using a rat ischemia-reperfusion injury model. Saline-treated kidneys exhibited increased tubular apoptosis with interstitial expression of alpha-smooth muscle actin (alpha-SMA), while EPO treatment inhibited tubular apoptosis and alpha-SMA expression to some extent. On the other hand, CEPO-treated kidneys showed minimal tubular apoptosis with limited expression of alpha-SMA. Moreover, CEPO significantly promoted tubular epithelial cell proliferation without erythropoiesis. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury.
Imamura
Ryoichi
R
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Isaka
Yoshitaka
Y
Ichimaru
Naotsugu
N
Takahara
Shiro
S
Okuyama
Akihiko
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004920:Erythropoiesis; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009395:Nephritis, Interstitial / Q000517:prevention & control; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
C494043:Ets1 protein, rat; D050784:Proto-Oncogene Protein c-ets-1; C488171:carbamylated erythropoietin; D004921:Erythropoietin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt