Department of Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
Eur Surg Res. 2024;65(1):83-94. doi: 10.1159/000539980. Epub 2024 Aug 2.
The aim of this present work was to investigate the mechanism of the microRNA (miR)-216a-5p/FASL axis in mice with acute kidney injury (AKI).
Mice kidney ischemia/reperfusion (I/R) injury was used as AKI models in this study. I/R mice were injected with miR-216a-5p- and FASL-related constructs to investigate potential mechanisms of kidney protection. Kidney function, inflammation, oxidative stress, and kidney cell apoptosis were assessed after 24 h of reperfusion. In vitro, the hypoxia-reoxygenation (H/R) model was used with kidney tubular epithelial cells (TECs) to mimic kidney I/R injury. H/R-treated TECs were transfected with miR-216a-5p- and FASL-related constructs to detect cell viability, inflammation, and oxidative stress. MiR-216a-5p and FASL expression levels in mouse kidney tissues and in H/R-treated TECs were detected.
MiR-216a-5p was downregulated and FASL was upregulated in kidney tissues of I/R mice and H/R-treated TECs. Upregulating miR-216a-5p attenuated kidney cell apoptosis and the damage of kidney function, and reduced inflammatory factor levels and oxidative stress response in kidney tissues of I/R mice. Upregulating miR-216a-5p advanced cell viability and reduced inflammatory factor levels and oxidative stress response in H/R-treated TECs. Downregulation of FASL effectively reversed the influences of downregulation of miR-216a-5p on kidney injury in mice and kidney TEC survival.
Our study reveals that miR-216a-5p reduces I/R-induced pathological kidney damage in AKI via suppressing FASL.
本研究旨在探讨微小 RNA（miR）-216a-5p/FASL 轴在急性肾损伤（AKI）小鼠中的作用机制。
本研究采用小鼠肾缺血/再灌注（I/R）损伤模型。通过注射 miR-216a-5p 和 FASL 相关构建物来研究肾脏保护的潜在机制。在再灌注 24 小时后评估肾功能、炎症、氧化应激和肾小管上皮细胞（TEC）凋亡。在体外，使用肾小管上皮细胞（TEC）模拟肾 I/R 损伤的缺氧/复氧（H/R）模型。用 miR-216a-5p 和 FASL 相关构建物转染 H/R 处理的 TEC，检测细胞活力、炎症和氧化应激。检测小鼠肾脏组织和 H/R 处理的 TEC 中 miR-216a-5p 和 FASL 的表达水平。
在 I/R 小鼠肾脏组织和 H/R 处理的 TEC 中，miR-216a-5p 下调，FASL 上调。上调 miR-216a-5p 可减轻 I/R 小鼠肾脏细胞凋亡和肾功能损伤，并降低肾脏组织中炎症因子水平和氧化应激反应。上调 miR-216a-5p 可提高 H/R 处理的 TEC 的细胞活力，并降低炎症因子水平和氧化应激反应。下调 FASL 可有效逆转 miR-216a-5p 下调对小鼠肾脏损伤和肾脏 TEC 存活的影响。
本研究表明，miR-216a-5p 通过抑制 FASL 减轻 I/R 诱导的 AKI 病理性肾损伤。
