Macrophage-derived exosomal lncRNA MSTRG.91634.7 inhibits fibroblasts activation by targeting PINK1 in silica-induced lung fibrosis

Silicosis is a fibrotic lung disease caused by the inhalation of free crystalline silica. Its pathogenesis is extremely complex and involves a variety of cells. Exosomes emerge as a favorable candidate for communication between cells. LncRNA is a major component transported by exosomes in many infla...

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Veröffentlicht in:Toxicology letters 2023-01, Vol.372, p.36-44
Hauptverfasser: Ban, Jiaqi, Liu, Fangwei, Zhang, Qi, Chang, Shuai, Zeng, Xinning, Chen, Jie
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Sprache:eng
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Zusammenfassung:Silicosis is a fibrotic lung disease caused by the inhalation of free crystalline silica. Its pathogenesis is extremely complex and involves a variety of cells. Exosomes emerge as a favorable candidate for communication between cells. LncRNA is a major component transported by exosomes in many inflammatory diseases. However, the role of exosomal lncRNA in the pathogenesis of silicosis is still unclear. In this study, the decreased expression of a novel exosomal lncRNA MSTRG.91634.7 in silicosis patients was identified according to high-throughput sequencing. Then, this macrophage-derived exosomal lncRNA MSTRG.91634.7 could regulate the fibroblast’s activation by targeting PINK1 in a co-culture system of THP-1 and MRC-5. Finally, the mouse was exposed to 3 mg/50 μL silica to set up the silicosis model. AAV-ov-Pink1 was intratracheally injected to overexpress PINK1 in mice lungs. Our results suggested that PINK1, the target protein of lncRNA MSTRG.91634.7, participated in restricting the silica-induced lung inflammation and fibrosis in mice. •A novel lncRNA MSTRG.91634.7 with decreased expression was found in peripheral exosome in silicosis patients.•Macrophage-derived exosomal lncRNA MSTRG.91634.7 could inhibit the activation of fibroblasts through targeting PINK1.•Overexpressing PINK1 repressed silica-induced lung inflammation and fibrosis in mice.
ISSN:0378-4274
1879-3169
DOI:10.1016/j.toxlet.2022.10.004