Targeting p16-induced senescence prevents cigarette smoke-induced emphysema by promoting IGF1/Akt1 signaling in mice Academic Article uri icon

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abstract

  • Senescence is a mechanism associated with aging that alters tissue regeneration by depleting the stem cell pool. Chronic obstructive pulmonary disease (COPD) displays hallmarks of senescence, including a diminished stem cell population. DNA damage from cigarette smoke (CS) induces senescence via the p16 pathway. This study evaluated the contribution of p16 to CS-associated lung pathologies. p16 expression was prominent in human COPD lungs compared with normal subjects. CS induces impaired pulmonary function, emphysema, and increased alveolar epithelial cell (AECII) senescence in wild-type mice, whereas CS-exposed p16-/- mice exhibit normal pulmonary function, reduced emphysema, diminished AECII senescence, and increased pro-growth IGF1 signaling, suggesting that improved lung function in p16-/- mice was due to increased alveolar progenitor cell proliferation. In conclusion, our study suggests that targeting senescence may facilitate alveolar regeneration in COPD emphysema by promoting IGF1 proliferative signaling.

authors

  • Cottage, Christopher T
  • Peterson, Norman
  • Kearley, Jennifer
  • Berlin, Aaron
  • Xiong, Ximing
  • Huntley, Anna
  • Zhao, Weiguang
  • Brown, Charles
  • Migneault, Annik
  • Zerrouki, Kamelia
  • Criner, Gerald
  • Kolbeck, Roland
  • Connor, Jane
  • Lemaire, Raphael

publication date

  • December 2019