Department of Infection, Immunity and Inflammation, College of Life Sciences, University of Leicester, Leicester, United Kingdom.
College of Medicine, University of Kufa, Najaf, Iraq.
Curr Gene Ther. 2017;17(6):411-423. doi: 10.2174/1566523218666180214093043.
Renal Ischemia-Reperfusion Injury (IRI) is one of the main causes of Acute Kidney Injury (AKI), and may lead to chronic kidney disease. The high mortality rate of AKI has not changed in the last 5 decades due to non-recognition, nephrotoxin exposure, delayed diagnosis and lack of specific intervention. Complement activation plays important roles in IRI-induced AKI because of its association with immunity, inflammation, cell death and tissue repair. Nevertheless, the role of complement properdin, the sole positive regulator of the alternative pathway, in IRI-induced AKI has not been well defined. This review evaluates the dynamic changes and underlying mechanisms of complement activation with a focus on properdin in both in vitro and in vivo models challenged by hypoxia/ reoxygenation and renal IRI. The multiple actions of properdin associated with HMGB1 and caspase-3, apoptosis and inflammation mediators, are discussed in the context of immunity, injury and repair at both the early and later stages of AKI. The complement activation-independent role of properdin and the effect of modulating properdin with or without genotype alteration are also addressed. Taking together, these might provide new mechanistic insights that potentially benefit timely diagnosis and specific intervention of IRI-induced AKI.
肾缺血再灌注损伤 (IRI) 是急性肾损伤 (AKI) 的主要原因之一，可能导致慢性肾脏病。由于认识不足、肾毒性物质暴露、诊断延迟和缺乏特异性干预，过去 50 年来 AKI 的高死亡率并未改变。补体激活在 IRI 诱导的 AKI 中发挥重要作用，因为它与免疫、炎症、细胞死亡和组织修复有关。然而，补体固有因子作为替代途径的唯一正调节剂，在 IRI 诱导的 AKI 中的作用尚未得到很好的定义。本综述评估了补体激活的动态变化和潜在机制，重点关注缺氧/复氧和肾 IRI 挑战的体外和体内模型中的固有因子。固有因子与 HMGB1 和 caspase-3、细胞凋亡和炎症介质的多种作用，在 AKI 的早期和晚期阶段，从免疫、损伤和修复的角度进行了讨论。还讨论了固有因子补体激活的非依赖性作用以及用或不用基因型改变调节固有因子的作用。综上所述，这些可能为 IRI 诱导的 AKI 的及时诊断和特异性干预提供新的机制见解。
