Long non-coding RNA SNHG1 promotes fibroblast-to-myofibroblast transition during the development of pulmonary fibrosis induced by silica particles exposure
Inhaling silica dust in the environment can cause progressive pulmonary fibrosis, then silicosis. Silicosis is the most harmful occupational disease in the world, so the study of the mechanism is of great significance for the prevention and treatment of silicosis. Long non-coding RNAs (lncRNAs) are...
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| Autores principales: | , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Elsevier
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/5bc1a2cbf07b473ba898b2fd2315a977 |
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| Sumario: | Inhaling silica dust in the environment can cause progressive pulmonary fibrosis, then silicosis. Silicosis is the most harmful occupational disease in the world, so the study of the mechanism is of great significance for the prevention and treatment of silicosis. Long non-coding RNAs (lncRNAs) are important players in the pathological process of fibrotic diseases. However, the function of specific lncRNA in regulating pulmonary fibrosis remains elusive. In this study, a mouse model of pulmonary fibrosis via intratracheal instillation of silica particles was established, and the differential expression of lnc-SNHG1 and miR-326 in lung tissues and TGF-β1-treated fibroblasts was detected by the qRT-PCR method. Short interfering RNA (siRNA) and plasmid were designed for knockdown or overexpression of lnc-SNHG1 in fibroblasts. MiRNA simulant was designed for overexpression of miR-326 in vivo and in vitro. Dual-luciferase reporter system, immunofluorescence, western blot, wound healing and transwell assay were performed to investigate the function and the underlying mechanisms of lnc-SNHG1. As a result, we found that lnc-SNHG1 was highly expressed in fibrotic lung tissues of mice and TGF-β1-treated fibroblasts. Moreover, the high expression of lnc-SNHG1 facilitated the migration and invasion of fibroblasts and the secretion of fibrotic molecules, while the low expression of lnc-SNHG1 exerted the opposite effects. Further mechanism studies showed that miR-326 was the potential target of lnc-SNHG1, and there is a negative correlation between the expression levels of lnc-SNHG1 and miR-326. Combined with mitigating fibrotic effects of miR-326 in a mouse model of silica particles exposure, we revealed that lnc-SNHG1 significantly sponged miR-326 and facilitated the expression of SP1, thus accelerating fibroblast-to-myofibroblast transition and synergistically promoting the development of pulmonary fibrosis. Our study uncovered a key mechanism by which lnc-SNHG1 regulated pulmonary fibrosis through miR-326/SP1 axis, and lnc-SNHG1 is a potential target for the prevention and treatment of silicosis. |
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