Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 12 May 2021 / Approved: 14 May 2021 / Online: 14 May 2021 (17:05:25 CEST)

A peer-reviewed article of this Preprint also exists.

Lucas, J.H.; Wang, Q.; Muthumalage, T.; Rahman, I. Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells. Toxics 2021, 9, 144. Lucas, J.H.; Wang, Q.; Muthumalage, T.; Rahman, I. Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells. Toxics 2021, 9, 144.

Journal reference: Toxics 2021, 9, 144
DOI: 10.3390/toxics9060144

Abstract

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 senes-cence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung dis-eases 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 (BEAS2B) to MWCNTs for up to 72 hours and demonstrate that MWCNTs increase reactive oxygen species production (ROS) accompanied by inhibition of cell growth and proliferation. In addition, exposure resulted in the increase of p21 protein and senes-cence associated β-galactosidase (SA β-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-β (TGF-β) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and γH2A.X Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNTs or TGF-β alone. Together, this suggests that the senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators in the surrounding microenvironment.

Subject Areas

MWCNT; senescence; pulmonary fibrosis; epithelial

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