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7269048 
Journal Article 
CircRNA-012091/PPP1R13B-mediated Lung Fibrotic Response in Silicosis via Endoplasmic Reticulum Stress and Autophagy 
Cheng, Y; Luo, W; Li, Z; Cao, M; Zhu, Z; Han, C; Dai, X; Zhang, W; Wang, J; Yao, H; Chao, J 
2019 
Yes 
American Journal of Respiratory Cell and Molecular Biology
ISSN: 1044-1549
EISSN: 1535-4989 
61 
3 
380-391 
English 
Silicosis is a progressive fibrotic disease of lung tissue caused by long-term inhalation of SiO2. However, relatively few studies of the direct effects of SiO2 on lung fibroblasts have been performed. PPP1R13B is a major member of the apoptosis-stimulating proteins of the p53 family, but its role in pulmonary fibrosis is unclear. To elucidate the role of PPP1R13B in the pathological process of silicosis, we explored the molecular mechanisms related to PPP1R13B and the functional effects of proliferation and migration of fibroblasts. Through lentivirus transfection, Western blotting, and fluorescent in situ hybridization experiments, we found that SiO2 downregulated circRNA-012091 (circ-012091) expression in lung fibroblasts and induced upregulation of downstream PPP1R13B. Transfection of L929 cells with PPP1R13B CRISPR NIC plasmid inhibited the upregulation of endoplasmic reticulum stress (ERS) and autophagy-related protein expression in lung fibroblasts treated with SiO2, and induced decreases in cell proliferation, migration, and viability. Transfection of L929 cells with the PPP1R13B CRISPR ACT plasmid induced increases in cell proliferation, migration, and viability. In addition, the ERS inhibitor salubrinal and the autophagy inhibitor 3-methyladenine inhibited the increased migration of L929 cells transfected with the PPP1R13B CRISPR ACT plasmid. These results suggest that PPP1R13B regulated by circ-012091 promotes the proliferation and migration of lung fibroblasts through ERS and autophagy, and plays a crucial role in the development of pulmonary fibrosis in silicosis. 
Apoptosis Regulatory Proteins; 0; RNA, Circular; Silicon Dioxide; 7631-86-9; Index Medicus; silicosis; PPP1R13B; autophagy; circ-012091; endoplasmic reticulum stress; RNA, Circular -- metabolism; Apoptosis -- drug effects; Cell Proliferation -- drug effects; Apoptosis Regulatory Proteins -- metabolism; Pulmonary Fibrosis -- drug therapy; Signal Transduction -- drug effects; Humans; Pulmonary Fibrosis -- pathology; Cell Movement -- drug effects; Fibroblasts -- metabolism; In Situ Hybridization, Fluorescence -- methods; Autophagy -- drug effects; Silicon Dioxide -- pharmacology; Lung -- pathology; Lung -- drug effects; Endoplasmic Reticulum Stress -- drug effects