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

• DOI: 10.1038/s42003-019-0532-1
• Publication Date: 2019-08-09T10:02:38Z
• Authors: Christopher T. Co...; Norman Peterson; Jennifer Kearley; Aaron Berlin; Ximing Xiong; Anna Huntley; Weiguang Zhao; Charles Brown; Annik Migneault; Kamelia Zerrouki; Gerald Criner; Roland Kolbeck; Jane Connor; Raphael Lemaire
• Keywords: Senescence

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 diminished population. DNA damage from cigarette smoke (CS) induces senescence via p16 pathway. This study evaluated contribution to CS-associated lung pathologies. expression was prominent in human COPD lungs compared normal subjects. CS impaired function, emphysema, and increased alveolar epithelial (AECII) wild-type mice, whereas CS-exposed −/− mice exhibit reduced AECII pro-growth IGF1 signaling, suggesting improved function due progenitor proliferation. In conclusion, our suggests targeting may facilitate emphysema promoting proliferative signaling.