Exosomal miR-552-3p isolated from BALF of patients with silicosis induces fibroblast activation

Background

Silica particles can cause silicosis, a disease characterized by diffuse fibrosis of the lungs. Various signaling pathways composed of different types of cells and cytokines are involved in the development of silicosis. Exosomes have become a research hotspot recently. However, the role of exosomal microRNA (miRNA) in silicosis remains unclear.

Methods

In this study, we generated exosomal miRNA sequences from exosomes isolated from bronchoalveolar lavage fluid (BALF) of silicosis patients and the control group by high-throughput sequencing. Functional annotation and analysis of miRNA identified key target miRNAs. Levels of target miRNAs were analyzed in patient and animal samples and cells. Effects of increased miRNA were assessed through protein levels in target signaling pathways in cells treated with silica, miRNA mimics, and inhibitors.

Results

Our study identified 40 up-regulated and 70 down-regulated miRNAs, with miR-552–3p and its putative target gene Caveolin 1 (CAV1) as targets for further research. We found that the levels of exosomal miR-552–3p increased in silicosis patients’ BALF samples, silicosis model mice, and A549 cells exposed to silica. Inhibition of miR-552–3p suppressed the expression of fibrosis markers. The increased miR-552–3p leads to the up-regulation of fibronectin and α-smooth muscle actin (α-SMA) and the suppression of caveolin 1 in fibroblast cells. Mitogen-activated protein kinase (MAPK) signaling pathways are activated in cells treated with silica and miR-552–3p mimics.

Conclusions

These results help to understand exosomal miRNA-mediated intercellular communication and its key role in fibroblast activation and silicosis.