Different microRNAs contribute to the protective effect of mesenchymal stem cell-derived microvesicles in LPS induced acute respiratory distress syndrome.

ABSTRACT

Objectives: The present study aimed to determine whether bone marrow mesenchymal stem cell-derived microvesicles (MSC MVs) were effective in restoring lung tissue structure, and to assess the potential role of miRNAs in the pathogenesis and progression of acute respiratory distress syndrome (ARDS). Materials and Methods: ARDS was induced by lipopolysaccharide in male C57BL/6 mice. The degree of lung injury was assessed by histological analysis, lung's wet weight/body weight, and protein levels in the bronchoalveolar lavage fluid (BALF). Sequencing was performed on the BGISEQ-500 platform. Differentially expressed miRNAs (DEMs) were screened with the DEGseq software. The target genes of DEMs were predicted by iRNAhybrid, miRanda, and TargetScan. Results: Compared with LPS-injured mice, MSC MVs reduced lung water and total protein levels in the BALF, demonstrating a protective effect. 52 miRNAs were differentially expressed following treatment with MSC MVs in ARDS mice. Among them, miR-532-5p, miR-223-3p, and miR-744-5p were significantly regulated. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed the target genes were mainly located in the cell, organelle, and membrane. Furthermore, KEGG pathways such as ErbB, PI3K-Akt, Ras, MAPK, Toll, and Wnt signaling pathways were the most significant pathways enriched by the target genes. Conclusion: MSC MVs treatment was involved in alleviating lung injury and promoting lung tissue repair by dysregulated miRNAs.