miRNA-1246 suppresses acute lung injury-induced inflammation and apoptosis via the NF-κB and Wnt/β-catenin signal pathways

Abstract

Acute lung injury (ALI) is the common and complicated inflammatory lung disease. MicroRNAs (miRNA) have emerged as novel gene regulatory molecules which play a crucial role in multiple complicated diseases, including ALI. In this study, we aims to identify potential regulatory functions of miRNA-1246 in lipopolysaccharide (LPS)-induced ALI. In ALI mice, miRNA-1246 expression is effectively up-regulated, compared with the control group. miRNA-1246 overexpression effectively increases inflammation and apoptosis of in vitro ALI model. In contrast, miRNA-1246 knockdown effectively inhibits inflammation and cell apoptosis in vitro ALI model. Furthermore, up-regulation of miRNA-1246 significantly induces nuclear factor-kappa B (NF-κB) protein expression, and suppresses Wnt and β-catenin protein expression in vitro ALI model. Following the inhibition of NF-κB or Wnt/β-catenin signal using inhibitors, miRNA-1246 shows no significant effects on ALI-induced inflammation and apoptosis. Taken together, miRNA-1246 mediates ALI-induced lung inflammation and apoptosis via the NF-κB activation and Wnt/β-catenin suppression.

Keywords: ALI; Apoptosis; Inflammation; NF-κB; Wnt/β-catenin; miRNA-1246.