Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling
| Autor: | Yaqian Li, Shumin Li, Fang Yang, Shifeng Li, Fuyu Jin, Dingjie Xu, Na Mao, Wenchen Cai, Xue Yi, Hong Xu, Zhongqiu Wei, Heliang Liu, Xuemin Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
transforming growth factor Article fibroblast 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Silicosis silicosis Drug Discovery Pulmonary fibrosis microRNA medicine myocardin-related transcription factor Fibroblast Lung business.industry lcsh:RM1-950 medicine.disease myofibroblast lcsh:Therapeutics. Pharmacology 030104 developmental biology medicine.anatomical_structure response serum factor 030220 oncology & carcinogenesis Cancer research Molecular Medicine business Myofibroblast Transforming growth factor |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 20, Iss, Pp 851-865 (2020) |
| ISSN: | 2162-2531 |
| Popis: | To identify potential therapeutic targets for pulmonary fibrosis induced by silica, we studied the effects of this disease on the expression of microRNAs (miRNAs) in the lung. Rattus norvegicus pulmonary silicosis models were used in conjunction with high-throughput screening of lung specimens to compare the expression of miRNAs in control and pulmonary silicosis tissues. A total of 70 miRNAs were found to be differentially expressed between control and pulmonary silicosis tissues. This included 41 miRNAs that were upregulated and 29 that were downregulated relative to controls. Among them, miR-292-5p, miR-155-3p, miR-1193-3p, miR-411-3p, miR-370-3p, and miR-409a-5p were found to be similarly altered in rat lung and transforming growth factor (TGF)-β1-induced cultured fibroblasts. Using miRNA mimics and inhibitors, we found that miR-1193-3p, miR-411-3p, and miR-370-3p exhibited potent anti-fibrotic effects, while miR-292-5p demonstrated pro-fibrotic effects in TGF-β1-stimulated lung fibroblasts. Moreover, we also found that miR-411-3p effectively reduced pulmonary silicosis in the mouse lung by regulating Mrtfa expression, as demonstrated using biochemical and histological assays. In conclusion, our findings indicate that miRNA expression is perturbed in pulmonary silicosis and suggest that therapeutic interventions targeting specific miRNAs might be effective in the treatment of this occupational disease. Graphical Abstract Using high-throughput screening, Gao et al. found that 70 miRNAs were differentially expressed after chronic exposure to silica dust in rats. Moreover, they also showed that miR-411-3p could significantly attenuate pulmonary silicosis by inhibiting the Mrtfa gene. These results suggest that therapeutic interventions targeting specific miRNAs might be effective in the treatment of this occupational disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|