Cellular senescence limits acute lung injury induced by mechanical ventilation

Jorge Blazquez-Prieto; Covadonga Huidobro; Ines Lopez-Alonso; Laura Amado-Rodriguez; Paula Martin-Vicente; Cecilia Lopez-Martinez; Irene Crespo; Cristina Pantoja; Pablo J Fernandez-Marcos; Manuel Serrano; Jacob I Sznajder; Guillermo M Albaiceta

The acute nature of our model of lung injury precludes the detection of senescent cells using the canonical marker SA-b-galactosidase due to the time required for its accumulation. To overcome these limitations, we developed an in vitro model of alveolar stretch using A549 cells. The amount of SA-b-galactosidase positive cells 72 hours after stretch was significantly higher than in those cells cultured in static conditions ( Figure 4A ). Concording with these data we found that expression of Tp53 ( Figure 4B ) and Cdkn1a ( Figure 4C ) are increased. These changes led to a cell cycle arrest, with an increase in the proportion of cells in the G0/G1 phase and a decrease in those in G2/M phase ( Figure 4D ). These results suggest that mechanical stretch per se may promote cell senescence.