Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senescence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung diseases such as pulmonary fibrosis (PF). However, the crosstalk between downstream pathways mediating fibrotic and senescent responses of MWCNTs is not well-defined. Here, we exposed human bronchial epithelial cells (BEAS-2B) to MWCNTs for up to 72 h and demonstrate that MWCNTs increase reactive oxygen species (ROS) production accompanied by inhibition of cell proliferation. In addition, MWCNT exposure resulted in the increase of p21 protein abundance and senescence associated beta-galactosidase (SA beta-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-beta (TGF-beta) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and gamma H2A.X. Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNT or TGF-beta alone. Together, our study suggests that the cellular senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators, such as TGF-beta in the surrounding microenvironment.

Automated summary

The study found that exposure to MWCNTs can lead to cellular senescence in human bronchial epithelial cells, with increased production of reactive oxygen species and inhibition of cell proliferation. Co-exposure with the cytokine TGF-beta further exacerbated cellular senescence, as indicated by increased levels of related proteins and significantly elevated production of fibronectin and plasminogen activator inhibitor.