MiR-497 Prevents Septic Kidney Injury and Improves Immune Function Through Inhibition of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Pathway

Abstract

Abnormal expression of miR-497 is related to the progression of septic renal injury. This study aimed to identify the protective effect of miR-497 on septic renal injury and immune function. We established a rat model of septic renal injury with sham-operated group and treated rats with culture solution of miR-497, gentianella acuta (positive control group), miR-497 plus JAK/STAT pathway agonist, and distilled water (model group). After treatment, urine output and renal histopathological changes were detected. Flow cytometry and RT-qPCR determined the levels of serum Scr, BUN, KIM-1, NGAL, IgG, IgA, and IgM, and evaluated the CD4+T, CD8+T, NK cell activity. Western blot assessed the activity of JAK/STAT signaling pathway. The model group and pathway agonist group had the highest 24-hour urine output, serum Scr, BUN, KIM-1, and NGAL levels, followed by miR-497 group and positive control group, and sham-operated group. The CD4+T, and NK cell activity was reduced with a drop in IgG, IgA, IgM levels in rats with septic renal injury, but treatment with miR-497 or gentianella acuta restored the cell activity and Ig levels and addition of JAK/STAT pathway agonist would further decrease the immune cell activity. There was no difference between the model group and pathway agonist group, miR-497 group and positive control group (p < 0.05). Following miR-497 group, and sham-operated group, the expression of miR-497 in model group, pathway agonist group, and positive control group was lowest (p < 0.05). As the expression of JAK and STAT did not vary among five groups (p > 0.05), we found highest expression of p-JAK and p-STAT levels in model group, positive control group, and pathway agonist group, and lowest expression in sham-operated group. miR-497 inhibits the activity of JAK/STAT signaling, up-regulates the activity of CD4+T, NK cells and levels of IgG, IgA, IgM, while inhibiting CD8+T cells activity to improve immune function. In conclusion, miR-497 attenuates septic kidney injury through inhibiting KIM-1 and NGAL expression, indicating that miR-497 and JAK/STAT pathways may be potential therapeutic targets for treating septic kidney injury.