Abstract
BackgroundSilicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis. Although great effort has been made to understand the pathogenesis of the disease, molecular mechanism underlying silicosis is not fully elucidated. This study was aimed to explore proteomic and transcriptomic changes in rat model of silicosis.MethodsTwenty male Wistar rats were randomly divided into two groups with 10 rats in each group. Rats in the model group were intratracheally instilled with 50 mg/mL silicon dioxide (1 mL per rat) and rats in the control group were treated with 1.0 mL saline (1 mL per rat). Twenty-eight days later, transcriptomic analysis by microarray and tandem mass tags (TMT)-based proteomic analysis were performed to reveal the expression of mRNAs and proteins in lung tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to analyze the altered genes and proteins. The integrated analysis was performed between transcriptome and proteome. The data were further verified by RT-qPCR and parallel reaction monitoring (PRM).ResultsIn total, 1769 differentially expressed genes (DEGs) and 650 differentially expressed proteins (DEPs) were identified between the silicosis model and control groups. The integrated analysis showed 250 DEPs were correlated to the corresponding DEGs (cor-DEPs-DEGs), which were mainly enriched in phagosome, leukocyte transendothelial migration, complement and coagulation cascades and cellular adhesion molecule (CAM). These pathways are interrelated and converged at common points to produce an effect. GM2a, CHI3L1, LCN2 and GNAI1 are involved in the extracellular matrix (ECM) and inflammation contributing to fibrosis.ConclusionOur comprehensive transcriptome and proteome data provide new insights into the mechanisms of silicosis and helpful information for more targeted prevention and treatment of silicosis.
Highlights
Silicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis
We evaluated key target genes and proteins and associated pathways involved in silicosis through an integrative analysis with mRNA microarray and tandem mass tags (TMT) data
Damaged alveolar structures, infiltrating inflammatory cells and silicotic nodule were observed in each rat from silica-treated group, which showed rat silicosis model was successfully replicated in this study
Summary
Silicosis is a systemic disease characterized by persistent inflammation and incurable pulmonary fibrosis. Great effort has been made to understand the pathogenesis of the disease, molecular mechanism underlying silicosis is not fully elucidated. Silicosis is a systemic disease characterized by persistent inflammation and progressive pulmonary fibrosis. Even if the exposure is terminated, silicosis can continue to develop and result in breath difficulty, low blood oxygen levels and eventual death [2, 3]. The exact molecular mechanism underlying the silicosis is not fully elucidated and there are no specific drugs that can effectively alleviate or reverse silica-induced lung injury. There is an urgent need to undersand the molecules and molecular pathways leading to silicosis
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