lncRNAPCAT29 inhibits pulmonary fibrosis via the TGF‑β1‑regulated RASAL1/ERK1/2 signal pathway.
MOLECULAR MEDICINE REPORTS(2018)
Abstract
Pulmonary fibrosis is a severe respiratory disease characterized by the aggregation of extracellular matrix components and inflammation-associated injury. Studies have suggested that long non-coding RNAs (lncRNA) may serve a role in the pathophysiological processes of pulmonary fibrosis. However, the potential molecular mechanisms involving the lncRNA, prostate cancer-associated transcript 29 (lncRNAPCAT29) in the progression of pulmonary fibrosis are yet to be determined. In the present study, the role of lncRNAPCAT29 and the potential signaling mechanism in pulmonary fibrosis progression was investigated. Reverse transcription-quantitative polymerase chain reaction and immunohistochemistry revealed that the expression levels of lncRNAPCAT29 were downregulated within interstitial lung cells from mice with silica-induced pulmonary fibrosis. Transfection with lncRNAPCAT29 was associated with upregulated expression of microRNA (miRNA)-221 and downregulated expression of transforming growth factor-1 (TGF-1); reduced inflammation and fibrotic progression was also associated with lncRNAPCAT29 transfection. TGF-1 expression levels were inhibited within pulmonary fibroblasts due to lncRNAPCAT29 expression; NEDD4 binding protein 2 and Plexin-A4 expression levels were also suppressed. Analysis of the potential mechanism underlying silica-induced pulmonary fibrosis revealed that the expression levels of RAS protein activator like 1 (RASAL1) and extracellular signal-regulated kinases 1/2 (ERK1/2) were suppressed due to lncRNAPCAT29 expression. The results of the present study demonstrated that lncRNAPCAT29 induced miRNA-221 upregulation and TGF-1 downregulation. These observations were associated with reduced inflammation and progression of silica-induced pulmonary fibrosis via the TGF-1-regulated RASAL1/ERK1/2 signaling pathway, which may serve as a potential target for the treatment of pulmonary fibrosis.
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Key words
pulmonary fibrosis,long non-coding RNA prostate cancer-associated transcript 29,inflammation,transforming growth factor-1,microRNA-221,RAS protein activator like 1,extracellular signal-regulated kinases 1/2
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