Identification of key pathways and genes in the progression of silicosis based on WGCNA

Abstract

Silicosis, induced by inhaling silica particles in workplaces, is one of the most common occupational diseases. The prognosis of silicosis and its consequent fibrosis is extremely poor due to limited treatment modalities and lack of understanding of the disease mechanisms. In this study, a Wistar rat model for silicosis fibrosis was established by intratracheal instillation of silica (0, 50, 100 and 200 mg/mL, 1 mL) with the evidence of Hematoxylin and Eosin (HE) and Masson staining and the expressions of inflammatory and fibrotic proteins of rats’ lung tissues. RNA of lung tissues of rats exposed to 200 mg/mL silica particles and normal saline for 14 d and 28 d was extracted and sequenced to detect differentially expressed genes (DEGs) and to identify silicosis fibrosis-associated modules and hub genes by Weighted gene co-expression network analysis (WGCNA). Predictions of gene functions and signaling pathways were conducted using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In this study, it has been demonstrated the promising role of the Hippo signaling pathway in silicosis fibrosis, which will be conducive to elucidating the specific mechanism of pulmonary fibrosis induced by silica and to determining molecular initiating event (MIE) and adverse outcome pathway (AOP) of silicosis fibrosis.

Keywords:

• Silicosis
• Pulmonary fibrosis
• RNA-seq
• Weighted gene co-expression network analysis (WGCNA)
• Hippo signaling pathway

Acknowledgements

We appreciate Shuang Du, Liang Zhang and Zhuhai Cui from Beijing Qinglian Biotech Co., Ltd for their help and technical support.

Disclosure statement

The authors declare that there is no conflict of interest.

Additional information

Funding

This work was supported by the Ministry of Science and Technology of the People’s Republic of China (2018ZX09711001-011) and the National Natural Science Foundation of China (No. 81773474).