Antioxidants prevent particulate matter-induced senescence of lung fibroblasts
Sein Jin1,2, Sung-Jin Yoon3, Na-Young Jung1,4
1Aging Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141, South Korea.
Abstract:
Particulate matter (PM) contributes to human diseases, particularly lung disease; however, the molecular mechanism of its action is yet to be determined. Herein, we found that prolonged PM exposure induced the cellular senescence of normal lung fibroblasts via a DNA damage-mediated response. This PM-induced senescence (PM-IS) was only observed in lung fibroblasts but not in A549 lung adenocarcinoma cells. Mechanistic analysis revealed that reactive oxygen species (ROS) activate the DNA damage response signaling axis, increasing p53 phosphorylation, ultimately leading to cellular senescence via an increase in p21 expression without affecting the p16-pRB pathway. A549 cells, instead, were resistant to PM-IS due to the PM-induced ROS production suppression. Water-soluble antioxidants, such as vitamin C and N-Acetyl Cysteine, were found to alleviate PM-IS by suppressing ROS production, implying that antioxidants are a promising therapeutic intervention for PM-mediated lung pathogenesis.
Insights
Particulate matter exposure causes lung fibroblast senescence through DNA damage. Antioxidants may treat lung disease by reducing this cellular aging.
Area of Science:
- Environmental Health
- Cell Biology
- Toxicology
Background:
- Particulate matter (PM) is linked to lung diseases, but its molecular mechanisms remain unclear.
- Cellular senescence, a state of irreversible growth arrest, is implicated in aging and disease.
- Understanding PM's cellular effects is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the molecular mechanisms by which particulate matter induces cellular senescence in lung fibroblasts.
- To identify differences in PM response between normal lung cells and lung cancer cells.
- To explore potential therapeutic interventions against PM-induced lung pathogenesis.
Main Methods:
- Exposure of normal lung fibroblasts and A549 lung adenocarcinoma cells to particulate matter.
- Assessment of cellular senescence markers, including p53 phosphorylation and p21 expression.
- Measurement of reactive oxygen species (ROS) production.
- Evaluation of antioxidant effects (Vitamin C, N-Acetyl Cysteine) on PM-induced senescence.
Main Results:
- Prolonged PM exposure induced cellular senescence in normal lung fibroblasts via a DNA damage response.
- PM-induced senescence (PM-IS) was mediated by ROS, leading to p53 phosphorylation and increased p21 expression.
- A549 lung adenocarcinoma cells showed resistance to PM-IS due to suppressed ROS production.
- Water-soluble antioxidants effectively alleviated PM-IS by reducing ROS levels.
Conclusions:
- Particulate matter induces cellular senescence in lung fibroblasts through ROS-mediated DNA damage.
- Antioxidants represent a potential therapeutic strategy for mitigating PM-induced lung pathogenesis.
- Differential cellular responses highlight the complexity of PM toxicity in lung tissue.
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