The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/β-catenin signaling

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.