Department of Urology, Renmin Hospital of Wuhan University, Wuhan, China.
Urol Int. 2021;105(7-8):687-696. doi: 10.1159/000515649. Epub 2021 May 7.
Renal ischemia/reperfusion (I/R) injury (RIRI) is the main cause of acute kidney injury (AKI) in patients. We investigated the role of miR-182 after renal ischemia/reperfusion (I/R) in rat to characterize the microRNA (miRNA) network activated during development and recovery from RIRI.
12 h after lethal (45 min) renal ischemia, AKI was verified by renal histology (tubular necrosis and regeneration), blood urea nitrogen level, and renal mRNA expression in Wistar rats. We found that miR-182 markedly increased after renal I/R. In cell hypoxia/reoxygenation model, we found similar upregulation of miR-182. In function gain/loss assay, we confirmed an impaired effect of miR-182 and identified Forkhead box O3 (FoxO3) as a direct downstream target of it. By using miR-182 antagomir, the I/R injury was markedly ameliorated.
Our results demonstrate that miR-182 promotes cell apoptosis and I/R injury through directly binding to FoxO3. The present study will provide potential therapeutic targets for renal I/R-induced AKI, and open a new avenue for AKI treatment by manipulating miRNAs levels.
肾缺血/再灌注（I/R）损伤（RIRI）是导致患者急性肾损伤（AKI）的主要原因。我们研究了肾缺血/再灌注（I/R）后大鼠中 miR-182 的作用，以阐明在 RIRI 发展和恢复过程中激活的 miRNA（miRNA）网络。
在 Wistar 大鼠中，在致死性（45 分钟）肾缺血后 12 小时，通过肾组织学（肾小管坏死和再生）、血尿素氮水平和肾 mRNA 表达验证 AKI。我们发现肾 I/R 后 miR-182 明显增加。在细胞缺氧/复氧模型中，我们发现 miR-182 也有类似的上调。在功能增益/损失测定中，我们证实了 miR-182 的受损作用，并确定 Forkhead box O3（FoxO3）为其直接下游靶标。通过使用 miR-182 拮抗剂，I/R 损伤明显改善。
我们的结果表明，miR-182 通过直接结合 FoxO3 促进细胞凋亡和 I/R 损伤。本研究将为肾 I/R 诱导的 AKI 提供潜在的治疗靶点，并通过操纵 miRNA 水平为 AKI 治疗开辟新途径。
