首页|Exploring the key pathways of tetrandrine in the treatment of early silicosis based on bioinformatics and in vitro experiments
Exploring the key pathways of tetrandrine in the treatment of early silicosis based on bioinformatics and in vitro experiments
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Objective: Exploring the key pathways affecting the development of early silicosis based on bioinformatics and in vitro experiments. Method: Collecting differentially expressed genes in silicosis patients through literature mining; Collecting differentially expressed genes in silicon dioxide infusion mice by using a high-throughput gene expression database (GEO); Obtaining disease targets related to silicosis by means of online human Mendelian genetic database (OMIM), GeneCards and comparative toxicgenomics database (CTD); differentially expressed genes and disease targets were subjected to gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis via R-package and Metascape platforms, respectively. The Schrödinger and Pymol software were used for molecular docking and modification. Silicon dioxide-stimulated macrophages and epithelial cells were modeled and analyzed by PCR and western blot (WB). Result: 2065 differentially expressed genes in silicosis patients, 2291 differentially expressed genes in rat infused with silicon dioxide, and 803 targets for silicosis-related diseases were screened out. GO enrichment analysis mainly involves G protein-coupled receptor binding, the regulation of inflammatory response, and participation in immune response. The enrichment analysis of KEGG pathway mainly included ECM-receptor interaction, TNF signaling pathway, and IL-17 signaling pathway. IL-17 signaling pathway was screened out from different genes and disease targets, indicating that IL-17 signaling pathway might be the key pathway for the development of silicosis. Molecular docking results showed that the silicosis drug tetrandrine had good binding effect with the RAF/MEK/ERK pathway in the IL-17 signaling pathway. Cellular experiments showed that tetrandrine reduced the expression of inflammatory factors such as IL-6 and TGF-β in macrophages by regulating the RAF/MEK/ERKpathway, and inhibited the epithelial-mesenchymal transition and expression of inflammatory factors in epithelial cells. Conclusion: Tetrandrine regulates the inflammatory response and epithelial-mesenchymal transition (EMT) through the RAF/MEK/ERK pathway and thus affects the early progression of silicosis.
School of Medicine,Anhui University of Science and Technology,Huainan 232001,China
Department of Clinical Laboratory,Gengjiu Hospital of Anhui Zhongke,Hefei 232001,China
Affiliated Cancer Hospital of Anhui University of Science and Technology/Huainan Oriental Hospital Group Cancer Hospital,Huainan 232001,China
Anhui Occupational Health and Safety Engineering Laboratory,Huainan 232001,China
Key Laboratory of Advanced Industrial Dust Purification and Occupational Health and Safety of Education Department,Huainan 232001,China
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国家自然科学基金Anhui University Collaborative Innovation ProjectAnhui University of Science and Technology Innovation and Entrepreneurship ProjectAnhui University of Science and Technology Innovation and Entrepreneurship ProjectAnhui University of Science and Technology Innovation and Entrepreneurship Project
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