Carbamylated Erythropoietin Ameliorates Cyclosporine Nephropathy Without Stimulating Erythropoiesis
Carbamylated Erythropoietin Ameliorates Cyclosporine Nephropathy Without Stimulating Erythropoiesis
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DOI：
10.3727/096368911x605501
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Okuyama, Akihiko
中科院分区：
文献类型：
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作者：
Abe, Toyofumi;Isaka, Yoshitaka;Okuyama, Akihiko
环孢素（CsA）的引入提高了移植物的存活率，但它会引起肾病，这限制了其临床应用。最近，我们报道了氨甲酰促红细胞生成素（CEPO）和EPO对肾脏缺血再灌注损伤的保护作用。为了研究CEPO的临床应用，我们接下来用csa肾病模型评估了CEPO的长期治疗效果。CsA引起肾功能不全，而EPO/CEPO可显著改善肾功能。EPO处理显著增加Hb浓度，而CEPO处理既不增加也不降低Hb浓度。CsA处理可诱导小管凋亡，而EPO/CEPO处理可抑制小管凋亡，增加PI3激酶活化和Akt磷酸化。同时，形态学评估显示EPO/CEPO显著减少csa诱导的间质纤维化，抑制间质巨噬细胞浸润。此外，实时RT-PCR显示，EPO/CEPO组皮质tgf - β 1和I型胶原mRNA水平受到抑制。这些结果提示使用CEPO保护肾脏免受csa引起的肾病是一种新的治疗方法。
The introduction of cyclosporine (CsA) has improved graft survival, but it causes nephropathy, which limits its clinical utility. 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 CsA-induced nephropathy model. CsA caused renal dysfunction, while EPO/CEPO administration significantly improved renal function. EPO treatment significantly increased Hb concentration, while CEPO treatment neither enhanced nor reduced Hb concentration. CsA treatment induced tubular apoptosis, while EPO/CEPO administration inhibited it and increased PI3 kinase activation and Akt phosphorylation. In parallel, morphological assessment revealed that EPO/CEPO significantly reduced CsA-induced interstitial fibrosis and inhibited interstitial macrophage infiltration. In addition, real-time RT-PCR demonstrated that cortical mRNA levels of TGF-beta 1 and type I collagen were suppressed in the EPO/CEPO group. These results suggest a new therapeutic approach using CEPO to protect kidneys from CsA-induced nephropathy.