Nonerythropoietic derivative of erythropoietin protects against tubulointerstitial injury in a unilateral ureteral obstruction model
Nonerythropoietic derivative of erythropoietin protects against tubulointerstitial injury in a unilateral ureteral obstruction model
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DOI：
10.1093/ndt/gfm842
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发表时间：
2008-05-01
影响因子：
6.1
通讯作者：
Imai, Enyu
中科院分区：
文献类型：
--
作者：
Kitamura, Harumi;Isaka, Yoshitaka;Imai, Enyu
背景促红细胞生成素（EPO）是细胞因子I型超家族的成员，主要通过防止红系祖细胞的凋亡来增加循环红细胞，已知其保护组织并且可以提高血红蛋白（Hb）浓度。最近，已经报道了包含EPO受体和β-共同受体的EPO的第二受体介导EPO诱导的组织保护。氨甲酰化修饰的EPO（CEPO）仅通过第二种受体发出信号。因此，我们假设CEPO治疗不会增加Hb浓度，但可以防止肾小管损伤，从而抑制肾小管间质损伤。方法。采用大鼠单侧输尿管梗阻模型评价CEPO的治疗作用。CEPO减少肾小管细胞凋亡和α-平滑肌肌动蛋白（α SMA）表达的情况下，红细胞增多症，而未经处理的梗阻性肾脏表现出增加肾小管细胞凋亡与扩大（α SMA）的表达。EPO治疗同样抑制肾小管细胞凋亡和α SMA表达，EPO治疗增加Hb浓度并诱导楔形梗死。我们建立了一种使用CEPO的治疗方法，以防止肾小管间质损伤。这种方法的治疗价值值得进一步关注和临床前研究。
Background. Erythropoietin (EPO), a member of the cytokine type I superfamily, acts to increase circulating erythrocytes primarily by preventing apoptosis of erythroid progenitors, is known to protect tissues and can raise haemoglobin (Hb) concentrations. Recently, a second receptor for EPO comprising the EPO receptor and beta-common receptor has been reported to mediate EPO-induced tissue protection. EPO modified by carbamylation (CEPO) only signals through this second receptor. Accordingly, we hypothesized that treatment with CEPO, which would not increase Hb concentrations, would protect against tubular damage and thereby inhibit tubulointerstitial injuries.Methods. We evaluated therapeutic effects of CEPO using a rat unilateral ureteral obstruction model.Results. CEPO decreased tubular apoptosis and alpha-smooth muscle actin (alpha SMA) expression in the absence of polycythaemia, while the untreated obstructed kidneys exhibited increased tubular apoptosis with expanded (alpha SMA) expression. While EPO treatment similarly inhibited tubular apoptosis and alpha SMA expression, EPO treatment increased Hb concentrations and induced a wedge-shaped infarction.Conclusion. We established a therapeutic approach using CEPO to protect against tubulointerstitial injury. The therapeutic value of this approach warrants further attention and preclinical studies.