MicroRNA‑129 plays a protective role in sepsis‑induced acute lung injury through the suppression of pulmonary inflammation via the modulation of the TAK1/NF‑κB pathway.

Excessive inflammatory response and apoptosis play key roles in the pathogenic mechanisms of sepsis‑induced 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 sepsis‑induced 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. miR‑129 was found to be the most significant miRNA, among the identified miRNAs. The upregulation of miR‑129 markedly alleviated LPS‑induced lung injury, as indicated by the decrease in lung permeability in and the wet‑to‑dry lung weight ratio, as well as the improved survival rate of mice with ALI administered miR‑129 mimic. Moreover, the upregulation of miR‑129 reduced pulmonary inflammation and apoptosis in mice with ALI. Of note, transforming growth factor activated kinase‑1 (TAK1), a well‑known regulator of the nuclear factor‑κB (NF‑κB) pathway, was directly targeted by miR‑129 in RAW 264.7 cells. More importantly, miR‑129 upregulation impeded the LPS‑induced activation of the TAK1/NF‑κB signaling pathway, as illustrated by the suppression of the nuclear phosphorylated‑p65, p‑IκB‑α and p‑IKKβ expression levels. Collectively, the findings of the present study indicate that miR‑129 protects mice against sepsis‑induced ALI by suppressing pulmonary inflammation and apoptosis through the regulation of the TAK1/NF‑κB signaling pathway. This introduces the basis for future research concerning the application of miR‑129 and its targets for the treatment of ALI.