Department of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark.
Int J Mol Sci. 2023 Oct 18;24(20):15312. doi: 10.3390/ijms242015312.
Acute kidney injury (AKI) is often caused by ischemia-reperfusion injury (IRI). IRI significantly affects kidney metabolism, which elicits pro-inflammatory responses and kidney injury. The ischemia/reperfusion of the kidney is associated with transient high mitochondrial-derived reactive oxygen species (ROS) production rates. Excessive mitochondrial-derived ROS damages cellular components and, together with other pathogenic mechanisms, elicits a range of acute injury mechanisms that impair kidney function. Mitochondrial-derived ROS production also stimulates epithelial cell secretion of extracellular vesicles (EVs) containing RNAs, lipids, and proteins, suggesting that EVs are involved in AKI pathogenesis. This literature review focuses on how EV secretion is stimulated during ischemia/reperfusion and how cell-specific EVs and their molecular cargo may modify the IRI process. Moreover, critical pitfalls in the analysis of kidney epithelial-derived EVs are described. In particular, we will focus on how the release of kidney epithelial EVs is affected during tissue analyses and how this may confound data on cell-to-cell signaling. By increasing awareness of methodological pitfalls in renal EV research, the risk of false negatives can be mitigated. This will improve future EV data interpretation regarding EVs contribution to AKI pathogenesis and their potential as biomarkers or treatments for AKI.
急性肾损伤（AKI）通常由缺血再灌注损伤（IRI）引起。IRI 会显著影响肾脏代谢，引发促炎反应和肾损伤。肾脏的缺血/再灌注与短暂的高线粒体来源的活性氧（ROS）产生速率有关。过多的线粒体来源的 ROS 会损害细胞成分，与其他致病机制一起，引发一系列急性损伤机制，损害肾脏功能。线粒体来源的 ROS 产生还会刺激上皮细胞分泌含有 RNA、脂质和蛋白质的细胞外囊泡（EVs），表明 EVs 参与 AKI 的发病机制。本文综述重点介绍了在缺血/再灌注过程中 EV 分泌是如何被刺激的，以及细胞特异性 EVs 和它们的分子货物如何改变 IRI 过程。此外，还描述了分析肾脏上皮细胞衍生 EVs 时的关键缺陷。特别是，我们将重点讨论在组织分析过程中肾脏上皮细胞 EVs 的释放是如何受到影响的，以及这可能如何混淆细胞间信号传递的数据。通过提高对肾脏 EV 研究中方法学缺陷的认识，可以降低假阴性的风险。这将改善未来关于 EVs 对 AKI 发病机制的贡献及其作为 AKI 生物标志物或治疗方法的潜在价值的 EV 数据解释。
