Lnc-IL7R alleviates PM 2.5 -mediated cellular senescence and apoptosis through EZH2 recruitment in chronic obstructive pulmonary disease.

Autor: Lee KY; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Ho SC; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan., Sun WL; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan., Feng PH; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan., Lin CW; Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Chen KY; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Chuang HC; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan., Tseng CH; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan., Chen TT; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan., Wu SM; Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. chitosan@tmu.edu.tw.; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. chitosan@tmu.edu.tw.
Jazyk: angličtina
Zdroj: Cell biology and toxicology [Cell Biol Toxicol] 2022 Dec; Vol. 38 (6), pp. 1097-1120. Date of Electronic Publication: 2022 Mar 18.
DOI: 10.1007/s10565-022-09709-1
Abstrakt: Background: Long-term exposure to PM 2.5 (particulate matter with an aerodynamic diameter of ≤ 2.5 μm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM 2.5 .
Methods: Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM 2.5 exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM 2.5 -treated cells. The levels of lnc-IL7R and cellular senescence-associated genes, namely p16 INK4a and p21 CIP1/WAF1 , were determined through lung tissue section staining. The effects of p16 INK4a or p21 CIP1/WAF1 regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM 2.5 . Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21 CIP1/WAF1 .
Results: Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM 2.5 exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM 2.5 . Lower lnc-IL7R expression in PM 2.5 -treated cells induced p16 INK4a and p21 CIP1/WAF1 expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM 2.5 -treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21 CIP1/WAF1 expression through epigenetic modulation.
Conclusion: Lnc-IL7R attenuates PM 2.5 -mediated p21 CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.
(© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
Databáze: MEDLINE
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