The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/β-catenin signaling
The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/β-catenin signaling
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DOI：
10.1016/j.jfma.2015.01.007
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发表时间：
2015-05-01
影响因子：
3.2
通讯作者：
Li, Bing
中科院分区：
文献类型：
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作者：
Chen, Xiao;Wang, Cen-Cen;Li, Bing
背景/目的：了解保护肾脏免受损伤的机制非常重要，因为没有有效的治疗方法可以促进修复，而且肾脏经常不能充分修复。有证据表明，促红细胞生成素（EPO）具有重要的肾脏保护作用，独立于其促红细胞生成作用。方法：采用成年雄性Sprague-Dawley大鼠建立肾缺血再灌注损伤（IRI）模型，观察EPO对肾脏的保护作用。随后在肾IRI后6小时随机用EPO或载体处理大鼠。在肾脏IRI后第3天、第5天和第7天处死大鼠。检测肾功能和组织学改变。通过免疫组化染色评价肾间质巨噬细胞浸润、细胞增殖、凋亡和血管生成。结果：EPO能显著改善肾功能，减轻肾小管损伤，并能显著提高肾功能，降低肾小管损伤程度。此外，EPO治疗显着防止肾小管细胞凋亡和促进细胞增殖后IRI。与溶媒相比，促红细胞生成素显著抑制巨噬细胞浸润。此外，用EPO治疗显著防止了微血管的损失。结论：促红细胞生成素通过抑制肾微血管和肾小管上皮细胞的损伤，促进Wnt/beta-catenin通路的激活，调节miR-21、-214、-210和-199a的表达，从而保护肾脏免受IRI的损伤。版权所有（C）2015，爱思唯尔台湾有限公司及台湾医学会. All rights reserved.
Background/purpose: Understanding the mechanisms of protecting the kidneys from injury is of great importance because there are no effective therapies that promote repair and the kidneys frequently do not repair adequately. Evidence has shown that erythropoietin (EPO) has a vital renoprotective role, independent of its erythropoietic effect. However, whether EPO can contribute to kidney repair after injury and the potential mechanisms are not fully understood.Methods: To investigate the renoprotective mechanism of EPO, a kidney ischemia/reperfusion injury (IRI) model was induced in adult male Sprague-Dawley rats. The rats were subsequently randomly treated with EPO or a vehicle 6 hours after the kidney IRI. The rats were sacrificed on Day 3, Day 5, and Day 7 post kidney IRI. Renal function and histological alterations were examined. Renal interstitial macrophage infiltration, cell proliferation, apoptosis, and angiogenesis were evaluated by immunostaining. Furthermore, the effects of EPO on the Wnt/beta-catenin pathway and IRI-related micro-RNAs were investigated.Results: The administration of EPO significantly improved renal function and reduced tubular injury. Furthermore, EPO treatment significantly prevented tubular cell apoptosis and promoted cell proliferation after IRI. Erythropoietin significantly suppressed macrophage infiltration, compared to the vehicle. In addition, treatment with EPO markedly prevented the loss of microvasculature. We have also demonstrated that, compared to the vehicle, EPO administration enhanced the expression of Wnt7b and beta-catenin, and downregulated miR-21, -214, -210, and -199a.Conclusion: Erythropoietin protects the kidneys against IRI by attenuating injury of the renal microvasculature and tubule epithelial cells, by promoting Wnt/beta-catenin pathway activation, and by regulating miRNA expression. Copyright (C) 2015, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.