RT Journal Article
SR Electronic
T1 Senescent human bronchial epithelial cells induce small airway fibrosis in mice
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA863
DO 10.1183/13993003.congress-2021.PA863
VO 58
IS suppl 65
A1 Nayuta Saito
A1 Fernanda Ines Hernandez
A1 Federico Pietrocola
A1 Manuel Serrano
YR 2021
UL http://erj.ersjournals.com/content/58/suppl_65/PA863.abstract
AB Introduction: Recent studies have shown that accelerated cellular senescence is pathologically involved in the mechanisms for chronic obstructive pulmonary disease (COPD) progression via impaired cell repopulation and prolonged inflammation partly conferred by senescence-associated secretory phenotype. Hence, preventing cellular senescence is thought to be a promising therapeutic modality for COPD. However, neither pathological mechanisms of senescent cells inducing COPD, nor the effects of eliminating senescent cells in COPD progression especially in vivo, are fully understood.Hypothesis: Intratracheal injection of human bronchial epithelial cells treated with cigarette smoke may recapitulate COPD in mice.Methods: To elucidate the effect of human senescent cells in vivo, we intratracheally injected senescent human bronchial epithelial cells to nude mice. Histopathological studies were performed to detect marker of senescence and fibrosis.Results: The accumulation of human P21 positive cells in peribronchiolar area are seen in mice injected with senescent cells. We obtained similar results with the senescence-associated β-gal positive cells, which show accumulation of senescent cells in peribronchiolar area. Also, we found peribronchiolar fibrosis, which is one of the main pathological findings in COPD.Conclusion: Senescent human bronchial epithelial cells accumulate in the peribronchial area, and cause small airway fibrosis. This model may represent the initial stages of COPD pathogenesis in mice, and be useful to study its origin and therapeutic approaches. This human cell-initiated COPD model might have advantages for drug screening.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA863.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).