Department of Nephrology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China.
Department of Nephrology, Siyang Hospital of Traditional Chinese Medicine, Suqian, Jiangsu, China.
J Cell Mol Med. 2022 Mar;26(6):1766-1775. doi: 10.1111/jcmm.16072. Epub 2020 Nov 16.
Renal ischaemia-reperfusion (RI/R) injury is one major pathological state of acute kidney injury (AKI) with a mortality rate ranking 50% to 80%. MiR-144-5p acts as a molecular trigger in various diseases. We presumed that miR-144-5p might be involved RI/R injury progression. We found that RI/R injury decreased miR-144-5p expression in rat models. MiR-144-5p downregulation promoted cell apoptosis rate and activated Wnt/β-catenin signal in RI/R injury rats. By performing bioinformatic analysis, RIP, RNA pull-down, luciferase reporter experiments, we found that circ-AKT3 sponged to miR-144-5p and decreased its expression in RI/R injury rats. Moreover, we found that circ-AKT3 promoted cell apoptosis rate and activated Wnt/β-catenin signal, and miR-144-5p mimic reversed the promotive effect of circ-AKT3 in rat models. We also found that circ-AKT3 increased the oxidative stress level in rat models. In conclusion, our study suggests that the circAKT3 is involved RI/R injury progression through regulating miR-144-5p/Wnt/β-catenin pathway and oxidative stress.
肾缺血再灌注（RI/R）损伤是急性肾损伤（AKI）的主要病理状态之一，死亡率高达 50%至 80%。miR-144-5p 在各种疾病中充当分子触发物。我们推测 miR-144-5p 可能参与 RI/R 损伤进展。我们发现 RI/R 损伤降低了大鼠模型中 miR-144-5p 的表达。miR-144-5p 的下调促进了 RI/R 损伤大鼠的细胞凋亡率并激活了 Wnt/β-catenin 信号。通过进行生物信息学分析、RIP、RNA 下拉、荧光素酶报告实验，我们发现 circ-AKT3 与 miR-144-5p 结合并降低了 RI/R 损伤大鼠中 miR-144-5p 的表达。此外，我们发现 circ-AKT3 促进了细胞凋亡率并激活了 Wnt/β-catenin 信号，而 miR-144-5p 模拟物逆转了大鼠模型中 circ-AKT3 的促进作用。我们还发现 circ-AKT3 增加了大鼠模型中的氧化应激水平。总之，我们的研究表明，circAKT3 通过调节 miR-144-5p/Wnt/β-catenin 通路和氧化应激参与 RI/R 损伤进展。
