A nonerythropoietic derivative of erythropoietin inhibits tubulointerstitial fibrosis in remnant kidney

作者：Imamura, Ryoichi; Isaka, Yoshitaka^*; Sandoval, Ruben M.; Ichimaru, Naotsugu; Abe, Toyofumi; Okumi, Masayoshi; Yazawa, Koji; Kitamura, Harumi; Kaimori, Jyunya; Nonomura, Norio; Rakugi, Hiromi; Molitoris, Bruce A.; Takahara, Shiro

来源：Clinical and Experimental Nephrology, 2012, 16(6): 852-862.

DOI：10.1007/s10157-012-0647-x

• Carbamylated erythropoietin
• Remnant kidney
• Apoptosis
• TGF-beta

The tissue-protective effects of erythropoietin (EPO) have been extensively investigated, and EPO administration can raise the hemoglobin (Hb) concentration. Recently, we reported that carbamylated erythropoietin (CEPO) protected kidneys from ischemia-reperfusion injury as well as EPO.
To investigate the clinical applications of CEPO, we next evaluated the long-term therapeutic effect of CEPO using a tubulointerstitial model rat. We randomized remnant kidney model rats to receive saline, EPO, or CEPO for 8 weeks.
CEPO- and EPO-treated rats had improved serum creatinine levels compared with saline-treated remnant kidney model rats, although the Hb level was significantly increased in EPO-treated rats. Two-photon microscopy revealed that EPO/CEPO significantly ameliorated tubular epithelial cell damage assessed by endocytosis. In addition, CEPO or EPO protected endothelial cells with a sustained blood flow rate. EPO or CEPO suppressed the number of TUNEL-positive apoptotic cells with weak alpha SMA staining. Furthermore, PCR analysis demonstrated that TGF-beta and type I collagen expression was attenuated in EPO- or CEPO-treated rats, accompanied by a significant decrease in interstitial fibrosis.
We established a long-term therapeutic approach to protect tubulointerstitial injury with CEPO, and thus, the therapeutic value of this approach warrants further attention and preclinical studies.

• 出版日期2012-12