Back to Search Start Over

MMP-3 activation is involved in copper oxide nanoparticle-induced epithelial-mesenchymal transition in human lung epithelial cells.

Authors :
Zhang, Yuanbao
Mo, Yiqun
Yuan, Jiali
Zhang, Yue
Mo, Luke
Zhang, Qunwei
Source :
Nanotoxicology. Dec2021, Vol. 15 Issue 10, p1380-1402. 23p.
Publication Year :
2021

Abstract

Copper oxide nanoparticles (Nano-CuO) are widely used in medical and industrial fields and our daily necessities. However, the biosafety assessment of Nano-CuO is far behind their rapid development. Here, we investigated the adverse effects of Nano-CuO on normal human bronchial epithelial BEAS-2B cells, especially determined whether Nano-CuO exposure would cause dysregulation of MMP-3, an important mediator in pulmonary fibrosis, and its potential role in epithelial-mesenchymal transition (EMT). Our results showed that exposure to Nano-CuO, but not Nano-TiO2, caused increased ROS generation, MAPKs activation, and MMP-3 upregulation. Nano-CuO-induced ROS generation was not observed in mitochondrial DNA-depleted BEAS-2B ρ0 cells, indicating that mitochondria may be the main source of Nano-CuO-induced ROS generation. Pretreatment of the cells with ROS scavengers or inhibitors or depleting mitochondrial DNA significantly attenuated Nano-CuO-induced MAPKs activation and MMP-3 upregulation, and pretreatment of cells with MAPKs inhibitors abolished Nano-CuO-induced MMP-3 upregulation, suggesting Nano-CuO-induced MMP-3 upregulation is through Nano-CuO-induced ROS generation and MAPKs activation. In addition, exposure of the cells to Nano-CuO for 48 h resulted in decreased E-cadherin expression and increased expression of vimentin, α-SMA, and fibronectin, which was ameliorated by MMP-3 siRNA transfection, suggesting an important role of MMP-3 in Nano-CuO-induced EMT. Taken together, our study demonstrated that Nano-CuO exposure caused mitochondrial ROS generation, MAPKs activation, and MMP-3 upregulation. Nano-CuO exposure also caused cells to undergo EMT, which was through Nano-CuO-induced dysregulation of ROS/MAPKs/MMP-3 pathway. Our findings will provide further understanding of the potential mechanisms involved in metal nanoparticle-induced various toxic effects including EMT and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17435390
Volume :
15
Issue :
10
Database :
Academic Search Index
Journal :
Nanotoxicology
Publication Type :
Academic Journal
Accession number :
155482662
Full Text :
https://doi.org/10.1080/17435390.2022.2030822