Exosomal miRNAs contribute to coal dust particle-induced pulmonary fibrosis in rats

Coal workers' pneumoconiosis (CWP) is a fatal occupational disease caused by inhalation of coal dust particles, which leads to progressive pulmonary fibrosis. Recently, as new signal carriers for intercellular communication, exosomal miRNAs have been validated in the pathogenesis of multiple diseases. However, the research on exosomal miRNAs in CWP is still in the preliminary stage. Here, using miRNA sequencing, exosomal miRNA profiles in bronchoalveolar lavage fluid (BALF) from rats with pulmonary fibrosis induced by coal dust particles were analyzed, and the underlying biological function of putative target genes was explored by GO term analysis and KEGG pathway enrichment analysis. According to the results, intratracheal instillation of coal dust particles can alter the exosomal miRNAs expression in the BALF of rats. Further bioinformatics analysis provided some clues to reveal their function in pathological process of pneumoconiosis. More importantly, we identified 4 differentially expressed exosomal miRNAs (miRNA-21-5p, miRNA-29a-3p, miRNA-26a-5p, and miRNA-34a-5p) by qRT-PCR and further verified the temporal changes in the expression of these exosomal miRNAs in animal models from 2 weeks to 16 weeks postexposure. In addition, we conducted a preliminary study on Smad7 as a potential target of miRNA-21-5p and found that exosomal miRNA 21-5p/Smad7 may contribute to the pul-monary fibrosis induced by coal dust particles. Our study confirmed the contribution of exosomal miRNAs to coal dust particle-induced pulmonary fibrosis and provided new insights into the pathogenesis of CWP.

Automated summary

Coal workers' pneumoconiosis (CWP) is a fatal occupational disease caused by inhalation of coal dust particles, leading to pulmonary fibrosis. Exosomal miRNAs have been found to play a role in the pathogenesis of various diseases, but their involvement in CWP is still in the preliminary stage. This study analyzed the expression of exosomal miRNAs in the bronchoalveolar lavage fluid of rats with coal dust-induced pulmonary fibrosis and investigated their biological functions. The results showed that coal dust particles altered the expression of exosomal miRNAs in rats. Four differentially expressed exosomal miRNAs were identified and their temporal changes were verified in animal models. Furthermore, a potential target gene, Smad7, was studied and its contribution to coal dust-induced pulmonary fibrosis was suggested. This study confirms the role of exosomal miRNAs in CWP and provides new insights into its pathogenesis.