miR-124/IRE-1 affects renal ischemia/reperfusion injury by regulating endoplasmic reticulum stress in renal tubular epithelial cells
Chenguang Ding, Meng Dou, Yuxiang Wang, Yang Li, Ying Wang, Jin Zheng, Li Xiao, Wujun Xue, Xiaoming Ding, Puxun Tian
Abstract
Acute kidney injury (AKI) refers to a clinical syndrome that occurs as a result of a rapid decline in renal function caused by multiple factors. Renal ischemia/reperfusion (I/R) injury is one of the main causes of AKI and has a high incidence and mortality. However, the specific pathogenesis of renal I/R injury is still unclear. In recent years, a major breakthrough has been made in the study of endoplasmic reticulum stress (ERS)-mediated apoptosis in I/R injury. It has been reported that miRNAs play protective roles in ischemic/reperfused organs, but the molecular mechanisms have not been investigated deeply. In this study, the renal I/R mouse model was used to explore the roles of miR-124 in ERS and in renal I/R injury. The western blot results showed that the expression levels of ERS-related proteins IRE-1α, XBP-1, and glucose-regulated protein 78 (GRP78) were significantly increased in the I/R model group when compared with those in the control group. Meanwhile, qPCR results showed that miR-124 expression was decreased in the I/R injury model, and overexpression of miR-124 using miR-124 mimics effectively reduced the expression of ERS-related proteins and alleviated renal I/R injury. In addition, luciferase reporter assay was performed, and the results showed that IRE-1α and miR-124 may have direct interaction. In conclusion, our data indicated that miR-124 was a negative regulator of ERS via binding to IRE-1α, ultimately conferring its protective effect on the kidney, which demonstrates the regulatory mechanism of miR-124 in renal I/R injury and provides new ideas and methods for the prevention and treatment of renal I/R injury.