High-mobility group box 1 promotes epithelial-to-mesenchymal transition in crystalline silica induced pulmonary inflammation and fibrosis

Jixuan Ma; Yiju Xu; Wei Li; Yun Zhou; Dongming Wang; Meng Yang; Bin Wang; Weihong Chen

doi:10.1016/j.toxlet.2020.05.016

High-mobility group box 1 promotes epithelial-to-mesenchymal transition in crystalline silica induced pulmonary inflammation and fibrosis

Toxicol Lett. 2020 May 17:330:134-143. doi: 10.1016/j.toxlet.2020.05.016. Online ahead of print.

Authors

Jixuan Ma¹, Yiju Xu¹, Wei Li¹, Yun Zhou¹, Dongming Wang¹, Meng Yang¹, Bin Wang¹, Weihong Chen²

Affiliations

¹ Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
² Department of Occupational & Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China. Electronic address: wchen@mails.tjmu.edu.com.

PMID: 32428545
DOI: 10.1016/j.toxlet.2020.05.016

Abstract

Silicosis is an inflammatory and fibrotic lung disease caused by prolonged inhalation of silica. The potential role of high-mobility group box-1 (HMGB-1) and its underlying mechanisms in silicosis remain unclear. In this study, intratracheal instillation of a silica suspension was used to establish silicosis in male C57BL/6 mice. To elucidate the effects of HMGB-1 on the pathogenesis of silicosis, we used HMGB-1 neutralizing antibody (anti-HMGB-1) and recombinant HMGB-1 (rmHMGB-1) to abrogate or increase the HMGB-1 levels, respectively. At days 7, 28, and 84, the accumulation of macrophages and neutrophils decreased by anti-HMGB-1 treatment. The expression levels of interleukin-6 and tumor necrosis factor-α in lung increased in response to silica exposure across three time points; anti-HMGB-1 could alleviate those expressions at day 28 and 84. In contrast, rmHMGB-1 aggravated this process. At days 28 and 84, the protein expression of fibronectin and col1a1 decreased in the silica + anti-HMGB-1 groups but increased in silica + rmHMGB-1 groups compared to mice with silica alone. Further study suggested that HMGB-1-mediated epithelial-mesenchymal transition participated in the development of silicosis. In conclusion, the findings demonstrate that HMGB-1 participates in the pathogenesis of silicosis and may represent a potential therapeutic target for the treatment of silicosis.

Keywords: Epithelial-Mesenchymal transition; High-mobility group box 1; Pulmonary fibrosis; Pulmonary inﬂammation; Silicosis.