MicroRNA-490-3p inhibits inflammatory responses in LPS-induced acute lung injury of neonatal rats by suppressing the IRAK1/TRAF6 pathway

Acute lung injury (ALI) is a main reason for neonatal death. Studying the molecular mechanism behind neonatal ALI is critical for the development of therapeutic strategies. The present study explored microRNA (miR)-490-3p-mediated regulatory effects on lipopolysaccharide (LPS)-induced neonatal ALI. Initially, LPS (10 mg/kg body weight) was injected to 3-8 day old neonatal SD rats to induce ALI, and LPS (100 ng/ml) was used to treat lung epithelial cells to construct an ALI model in vitro. Next, miR-490-3p, pro-inflammatory factors (that included IL-1 beta, IL-6 and TNF alpha), interleukin 1 receptor associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6) mRNA expression levels in lung tissues and epithelial cells were assessed via reverse transcription-quantitative PCR. In addition, miR-490-3p mimics were adopted to construct its overexpressed cell model, and Cell Counting Kit-8 and BrdU assays were conducted to assess cell viability. Furthermore, the miR-490-3p target, IRAK was predicted by bioinformatics analysis and verified via Dual-luciferase reporter gene assay. The results revealed that miR-490-3p was markedly downregulated in an LPS-induced rat ALI model, while IL-1 beta, IL-6, TNF alpha, IRAK1 and TRAF6 were all upregulated and negatively correlated with miR-490-3p expression. Moreover, overexpressed miR-490-3p significantly inhibited LPS-induced lung epithelial cell injury and inflammatory response. Mechanistically, miR-490-3p targeted and attenuated IRAK1 expression, which thus inactivated the LPS-mediated TRAF6/NF-kappa B pathway. Overall, the present study indicated that miR-490-3p overexpression significantly inhibited LPS-induced ALI and inflammatory responses by restricting the IRAK1/TRAF6 pathway.

Automated summary

The study demonstrated that miR-490-3p overexpression significantly inhibited LPS-induced ALI and inflammatory responses by targeting and attenuating IRAK1 expression, thus inactivating the LPS-mediated TRAF6/NF-kappa B pathway. MiR-490-3p was found to be downregulated in the LPS-induced ALI model, while pro-inflammatory factors and IRAK1 were upregulated, negatively correlated with miR-490-3p expression. Overexpression of miR-490-3p inhibited lung epithelial cell injury and inflammatory response.