Abstract
COPD is associated with elevated cellular senescence. COPD patients have increased markers of oxidative stress, which can drive cellular senescence. MiR34a is involved in the induction of cellular senescence by inhibiting the anti-aging molecules sirtuin1/-6. Extracellular vesicles (EV), including microvesicles and exosomes, can contain miRNA involved in the induction of cellular senescence. In response to oxidative stress and in senescent cells, EVs cargo is modified. However, the involvement of EVs in epithelial cell senescence remains unclear.
The aim is to characterise EV released by airway epithelial cells in response to oxidative stress and to assess their effect on epithelial cell senescence.
BEAS2B cells and primary small airway epithelial cells (SAEC) were stimulated with H2O2 (100μM) for 48h. EV were isolated and characterised by Western blot and micro-BCA. miRNA expression in EV and cells treated with EVs was determined by qRT-PCR.
In response to H2O2, epithelial cells release significantly more microvesicles (4.25μg/ml in medium condition and 6.42 μg/ml) in response to H2O2 and exosomes (1.89μg/ml in medium vs 4.13μg/ml) in response to H2O2. Microvesicles and exosomes produced by BEAS2B stimulated with H2O2 showed increased expression of miR34a (1.44 fold, n=4). Microvesicles produced by SAEC from COPD patients exhibit increased expression of miR34a compared to non-smokers (n=7 non-smoker, n=6 COPD).
These data suggest that epithelial cells produce extracellular vesicles enriched in miRNA involved in cellular senescence. Further exploration of EVs in senescence may provide useful biomarkers and targets for future COPD therapy.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA2696.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021