Overexpression of miR-92a attenuates kidney ischemia–reperfusion injury and improves kidney preservation by inhibiting MEK4/JNK1-related autophagy

作者：Ming Ma, Hui Li, Saifu Yin, Tao Lin, Turun Song · 发表于：Cellular & Molecular Biology Letters · 年份：2023 · DOI：10.1186/s11658-023-00430-3 · 被引用次数：23 · 研究领域：MicroRNA in disease regulation、Autophagy in Disease and Therapy、Organ Transplantation Techniques and Outcomes

BACKGROUND: Kidney ischemia-reperfusion injury is inevitable in kidney transplantation, and is essential for primary graft dysfunction and delayed graft function. Our previous study has proved that miR-92a could ameliorate kidney ischemia-reperfusion injury, but the mechanism has not been studied. METHODS: This study conducted further research on the role of miR-92a in kidney ischemia-reperfusion injury and organ preservation. In vivo, mice models of bilateral kidney ischemia (30 min), cold preservation after ischemia (cold preservation time of 6, 12, and 24 h), and ischemia-reperfusion (reperfusion time of 24, 48, and 72 h) were established. Before or after modeling, the model mice were injected with miR-92a-agomir through the caudal vein. In vitro, the hypoxia-reoxygenation of HK-2 cells was used to simulate ischemia-reperfusion injury. RESULTS: Kidney ischemia and ischemia-reperfusion significantly damaged kidney function, decreased the expression of miR-92a, and increased apoptosis and autophagy in kidneys. miR-92a agomir tail vein injection significantly increased the expression of miR-92a in kidneys, improved kidney function, and alleviated kidney injury, and the intervention before modeling achieved a better effect than after. Moreover, miR-92a agomir significantly reduced the apoptosis and autophagy in HK-2 cells induced by hypoxia, hypoxia-reoxygenation, and rapamycin, while miR-92a antagomir had opposite effects. Furthermore, mitogen-activated protein kinase, c-Jun ...