The Effect of Autophagy Induced by Mothers Against Decapentaplegic Homolog 3 (Smad3) Regulated by MicroRNA (miRNA)-23b on Renal Injury in Septic Rats

Abstract

This study intends to investigate the mechanism by how microRNA (miRNA)-23b alleviates kidney damage in septic rats. Herein, septic rat model, control group and sham-operated model were set up to assess kidney tissue damage. Tissues were extracted from the rats and isolated into cells. Then cells were transfected with plasmids expressing miR-23b followed by analysis of the expression of miR-23b, Smad3, TLR4, HMGB1 and autophagy-related proteins (LC3, beclin-1) by western blot and RT-qPCR. The level of TNF-α, IL-6 and BUN and SCr were elevated in the model group and decreased after upregulation of miR-23b with increased LC3-II, Smad3 and Beclin-1 expression. miR-23b mimic group showed highest miR-23b expression followed by miR-23b NC group and miR-23b inhibitor group. The levels of TLR4, and HMGB1 and positive rate of NF-κBp65 in miR-23b mimic group were significantly lower than those in miR-23b inhibitor group (p < 0.05). Importantly, miR-23b directly targeted Smad3 and inhibited its expression. In conclusion, overexpressed miR-23b induces autophagy by promoting Smad3 expression, alleviates kidney damage in septic rats, and reduces inflammation and inactivates NF-κB signaling pathway.