MicroRNA-19b Attenuates Sepsis-associated Acute Kidney Injury by Regulating Inflammation and Oxidative Stress

Sepsis serves as an inflammatory disease and results in severe acute kidney injury (AKI). MicroRNA-19b (miR-19b) has presented crucial function in multiple disorders. However, the effect of miR-19b on AKI is still obscure. Here, we tried to explore the role of miR-19b in AKI progression. The expression of miR-19b was repressed in AKI rat model and was induced by miR-19b mimic. Meanwhile, the phosphorylation levels of AMPK and mTOR were induced in AKI rat model, while the treatment of miR-19b mimic repressed the levels in the model. The kidney injury was induced in AKI rat model and miR-19b mimic repressed the phenotype, while the co-treatment of AMPK signaling activator A769662 reversed the effect of miR-19b in the model. Meanwhile, the enhanced levels of urine NGAL (uNGAL), urine Kim-1 (uKim-1), urea nitrogen (BUN), and serum creatinine (sCr) were suppressed by miR-19b mimic, while the treatment of A769662 rescued this effect in AKI rat model. The levels of ROS and MDA were induced in AKI rats and miR-19b mimic inhibited the levels, while the co-treatment of A769662 could rescue the phenotype in the rats. In addition, the GSH levels and SOD and CAT activity were repressed in AKI rat model, in which miR-19b mimic rescued the phenotype and co-treatment of A769662 was able to reverse the effect in the rats. The expression of TNF-alpha, IL6, IL-1 beta enhanced in AKI rats was repressed by miR-19b mimic, in which the treatment of A769662 reversed the effect in the rats. In addition, the apoptosis induced in AKI rats was inhibited by miR-19b mimic and the treatment of A769662 could reverse the effect in the model. Therefore, we concluded that miR-19b attenuated sepsis-associated AKI by regulating inflammation and oxidative stress via AMPK/mTOR signaling. MiR-19b may be employed as the potential targets for the treatment of AKI.