MicroRNA­129 plays a protective role in sepsis­induced acute lung injury through the suppression of pulmonary inflammation via the modulation of the TAK1/NF­κB pathway.

ABSTRACT

Excessive inflammatory response and apoptosis play key roles in the pathogenic mechanisms of sepsis­induced acute lung injury (ALI); however, the molecular pathways linked to ALI pathogenesis remain unclear. Recently, microRNAs (miRNAs/miRs) have emerged as important regulators of inflammation and apoptosis in sepsis­induced ALI; however, the exact regulatory mechanisms of miRNAs remain poorly understood. In the present study, the gene microarray dataset GSE133733 obtained from the Gene Expression Omnibus database was analyzed and a total of 38 differentially regulated miRNAs were identified, including 17 upregulated miRNAs and 21 downregulated miRNAs, in mice with lipopolysaccharide (LPS)­induced ALI, in comparison to the normal control mice. miR­129 was found to be the most significant miRNA, among the identified miRNAs. The upregulation of miR­129 markedly alleviated LPS­induced lung injury, as indicated by the decrease in lung permeability in and the wet­to­dry lung weight ratio, as well as the improved survival rate of mice with ALI administered miR­129 mimic. Moreover, the upregulation of miR­129 reduced pulmonary inflammation and apoptosis in mice with ALI. Of note, transforming growth factor activated kinase­1 (TAK1), a well­known regulator of the nuclear factor­κB (NF­κB) pathway, was directly targeted by miR­129 in RAW 264.7 cells. More importantly, miR­129 upregulation impeded the LPS­induced activation of the TAK1/NF­κB signaling pathway, as illustrated by the suppression of the nuclear phosphorylated­p65, p­IκB­α and p­IKKß expression levels. Collectively, the findings of the present study indicate that miR­129 protects mice against sepsis­induced ALI by suppressing pulmonary inflammation and apoptosis through the regulation of the TAK1/NF­κB signaling pathway. This introduces the basis for future research concerning the application of miR­129 and its targets for the treatment of ALI.