矽肺
Wnt信号通路
纤维化
尘肺病
肺纤维化
职业性肺病
上皮-间质转换
医学
癌症研究
连环蛋白
连环素
病理
免疫学
肺
化学
内科学
信号转导
生物化学
癌症
转移
作者
Yazhou Tian,Jiarui Xia,Yang Guo,Chao Li,Yuanmeng Qi,Kai Dai,Chenchen Wu,Yonghua Guo,Wu Yao,Changfu Hao
标识
DOI:10.1016/j.ecoenv.2022.114410
摘要
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.
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