MiR-216a alleviates LPS-induced acute lung injury via regulating JAK2/STAT3 and NF-κB signaling.

Abstract

MicroRNAs (miRNAs) play an important role in the progression of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Till now, little is known about the role of miR-216a in ALI/ARDS. In this study, patients with ARDS exhibited significantly higher interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels than healthy controls (P < 0.01). However, miR-216a expression in patients with ARDS was significantly lower than healthy controls (P < 0.05), and negatively correlated with 28-day survival rate. Similar effects were observed in LPS-treated mice and A549 cells. MiR-216a over-expression reduced LPS-induced IL-1β, IL-6 and TNF-α levels, and ameliorated lung permeability, and prolonged overall survival of ALI mice. Further, miR-216a over-expression inhibited LPS-induced apoptosis and autophagy. In addition, the janus kinase-2 (JAK2) was a direct target of miR-216a. Silencing of JAK2 partially aggravated miR-216a-inhibited inflammation injury. Besides, miR-216a obviously decreased the expressions of phosphorylated signal transducer and the activator of transcription 3 (p-STAT3), p-p56, and p-IκBα. In conclusion, miR-216a alleviates LPS-induced inflammatory injury via regulating JAK2/STAT3 and NF-κB signaling.