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-Kappa B 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-kappa B (NF-kappa B) 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-kappa B signaling pathway, as illustrated by the suppression of the nuclear phosphorylated-p65, p-I kappa B-alpha and p-IKK beta 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-kappa B signaling pathway. This introduces the basis for future research concerning the application of miR-129 and its targets for the treatment of ALI.