MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome

doi:10.5847/wjem.j.1920-8642.2021.01.009

Abstract

Abstract:

BACKGROUND: Acute respiratory distress syndrome (ARDS) causes substantial mortalities. Alveolar epithelium is one of the main sites of cell injuries in ARDS. As an important kind of microRNAs (miRNAs), microRNA-145 (miR-145) has been studied in various diseases, while its role in ARDS has not been investigated.

METHODS: Lipopolysaccharide (LPS) was intratracheally instilled to establish a rat ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF) were measured using rat tumor necrosis factor-α and interleukin-6 enzyme-linked immunosorbent assay kits (R&D Systems), and the pathological structures were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscope; the lung miR-145 messenger RNA (mRNA) was detected using quantitative polymerase chain reaction. Bioinformatics focused on the target genes and possible pathways of gene regulation.

RESULTS: A rat model of LPS-induced ARDS was successfully established. The miR-145 was down-regulated in the LPS-induced ARDS lung, and mitochondrial dysfunction was observed in alveolar epithelial cells, most obviously at 72 hours after LPS. TargetScan and miRDB databases were used to predict the target genes of miR-145. A total of 428 overlapping genes were identified, seven genes were associated with mitochondrial function, and Ogt, Camk2d, Slc8a3, and Slc25a25 were verified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, and Gene Ontology (GO) biological process was mainly enriched in signal transduction and transcription regulation.

CONCLUSIONS: The miR-145 is down-regulated in LPS-induced ARDS, and affects its downstream genes targeting mitochondrial functions.

Key words: MicroRNA-145, Mitochondrial function, Lipopolysaccharide, Acute respiratory distress syndrome, Rats

Yi Han, Su-cheng Mu, Jian-li Wang, Wei Wei, Ming Zhu, Shi-lin Du, Min Min, Yun-jie Xu, Zhen-ju Song, Chao-yang Tong. MicroRNA-145 plays a role in mitochondrial dysfunction in alveolar epithelial cells in lipopolysaccharide-induced acute respiratory distress syndrome[J]. World Journal of Emergency Medicine, 2021, 12(1): 54-60.

Figures/Tables 3

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