2. Academic Validation
  3. A2aR inhibits fibrosis and the EMT process in silicosis by regulating Wnt/β-catenin pathway

A2aR inhibits fibrosis and the EMT process in silicosis by regulating Wnt/β-catenin pathway

  • Ecotoxicol Environ Saf. 2022 Dec 12;249:114410. doi: 10.1016/j.ecoenv.2022.114410.
Yangyang Tian 1,  Jiarui Xia 1,  Guo Yang 1,  Chao Li 1,  Yuanmeng Qi 1,  Kai Dai 1,  Chenchen Wu 1,  Yonghua Guo 1,  Wu Yao 2,  Changfu Hao 3
Affiliations

Affiliations

  • 1 Department of Occupational and Environment Health, School of Public Health, Zhengzhou University, No.100 Science Avenue5, Zhengzhou 450001, Henan Province, PR China.
  • 2 Department of Occupational and Environment Health, School of Public Health, Zhengzhou University, No.100 Science Avenue5, Zhengzhou 450001, Henan Province, PR China. Electronic address: yaowu@zzu.edu.cn.
  • 3 Department of Occupational and Environment Health, School of Public Health, Zhengzhou University, No.100 Science Avenue5, Zhengzhou 450001, Henan Province, PR China. Electronic address: haochangfu@126.com.
PMID: 36516619 DOI: 10.1016/j.ecoenv.2022.114410
Abstract

Silicosis, a disease characterized by diffuse fibrosis of the lung tissue, is caused by long-term inhalation of free silica (SiO2) dust in the occupational environment and is currently the most serious occupational diseases of pneumoconiosis. Several studies have suggested that alveolar type Ⅱ epithelial cells (AEC Ⅱ) undergo epithelial-mesenchymal transition (EMT) as one of the crucial components of silicosis in lung fibroblasts. A2aR can play a critical regulatory role in fibrosis-related diseases by modulating the Wnt/β-catenin pathway, but its function in the EMT process of silicosis has not been explained. In this study, an EMT model of A549 cells was established. The results revealed that A2aR expression is reduced in the EMT model. Furthermore, activation of A2aR or suppression of the Wnt/β-catenin pathway reversed the EMT process, while the opposite result was obtained by inhibiting A2aR. In addition, activation of A2aR in a mouse silicosis model inhibited the Wnt/β-catenin pathway and ameliorated the extent of silica-induced lung fibrosis in mice. To sum up, we uncovered that A2aR inhibits fibrosis and the EMT process in silicosis by regulating the Wnt/β-catenin pathway. Our study can provide an experimental basis for elucidating the role of A2aR in the development of silicosis and offer new ideas for further exploration of interventions for silicosis.

Keywords

A2aR; EMT; Fibrosis; Silicosis; Wnt/β-catenin.

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