Carbamylated Erythropoietin Improves Angiogenesis and Protects the Kidneys From Ischemia-Reperfusion Injury

Authors: Imamura, Ryoichi¹; Okumi, Masayoshi¹; Isaka, Yoshitaka²; Ichimaru, Naotsugu¹; Moriyama, Toshiki³; Imai, Enyu⁴; Nonomura, Norio¹; Takahara, Shiro⁵; Okuyama, Akihiko¹

Source: Cell Transplantation, Volume 17, Numbers 1-2, 2008 , pp. 135-141(7)

Publisher: Cognizant Communication Corporation

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Abstract:

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, partly due to the increased peritubular capillaries. The therapeutic effect of CEPO was evaluated using an endothelial tube formation assay in vitro, and a rat ischemia-reperfusion injury model in vivo. EPO treatment showed the tendency of increased tube formation, while CEPO treatment induced more capillary-like formation than EPO. Ischemia-reperfusion-induced kidneys exhibited characteristic nuclei of apoptosis in tubular epithelial cells with decreased peritubular capillaries, while EPO treatment inhibited tubular apoptosis with preserved endothelial cells. Moreover, CEPO-treated kidneys showed minimal tubular apoptosis with increased peritubular capillary endothelial cells. In conclusion, we identified a new therapeutic approach using CEPO to protect kidneys from ischemia-reperfusion injury by promoting angiogenesis.

Keywords: Angiogenesis; Carbamylated erythropoietin; Ischemia-reperfusion injury; Kidney; Apoptosis

Document Type: Research article

Affiliations: 1: Department of Urology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan 2: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Nephrology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan 3: Health Care Center, Osaka University, Osaka 560-0043, Japan, Department of Nephrology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan 4: Department of Nephrology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan 5: Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Publication date: 2008-01-01

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Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

Carbamylated Erythropoietin Improves Angiogenesis and Protects the Kidneys From Ischemia-Reperfusion Injury

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