miR-145 plays a role in mitochondria dysfunction in alveolar epithelial cells in LPS-induced ARDS

Abstract Backgrounds: Acute respiratory distress syndrome (ARDS) causes substantial mortality worldwide. Alveolar epithelium is one of the main sites of cell injury in ARDS. MicroRNAs (miRNAs) are small noncoding RNA molecules that are recognized as endogenous physiological regulators of gene expression. As an important miRNA, miR-145 has been studied in various diseases, while its role in ARDS remains not investigated. Methods: Intratracheal instillation of LPS was used to establish ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF), lung wet/dry ratio as well as the pathological structures using H&E staining and Transmission electron microscope (TEM) was evaluated; lung miR-145 mRNA expression was detected using qPCR. And further bioinformatics was focused on the target genes and possible pathways of the gene regulation. Results: A rat model of LPS-induced ARDS was well established by intratracheal instillation of LPS. miR-145 was down-regulated in LPS-induced ARDS lung, and mitochondria dysfunction was observed in alveolar epithelial cells in ARDS lung, most obviously at 72h after LPS. TargetScan and MirDB were used to predict the target genes of miR-145, a total of 428 overlapping genes were identified, among which, 7 genes were associated with mitochondria function. The KEGG pathways were significantly enriched in MAPK signaling pathway and RAS signaling pathway, and the GO biological process terms were mainly enriched in gene binding, signal transduction, and regulation of transcription. Conclusions: The current work provided evidence between miR-145 and LPS-induced ARDS. Clearly, miR-145 was down-regulated in LPS induced lung injury, and resultant had impact on its downstream genes targeting mitochondria functions through MAPK and RAS signaling pathway.