Temporal analysis of lung injury induced by real-ambient PM2 .5 exposure in mice

Fine particulate matter (PM_2.5 ) has been shown to induce lung injury. However, the pathophysiological mechanisms of PM_2.5 -induced pulmonary injury after different exposure times are poorly understood. In this study, we exposed male ICR mice to a whole-body PM_2.5 inhalation system at daily mean concentration range from 92.00 to 862.00 μg/m³ for 30, 60, and 90 days. We found that following prolonged exposure to PM_2.5 , pulmonary injury was increasingly evident with significant histopathological alterations. Notably, the pulmonary inflammatory response and fibrosis caused by PM_2.5 after different exposure times were closely associated with histopathological changes. In addition, PM_2.5 exposure caused oxidative stress, DNA damage and impairment of DNA repair in a time-dependent manner in the lung. Importantly, exposure to PM_2.5 eventually caused Apoptosis in the lung through upregulation of cleaved-caspase-3 and downregulation of Bcl-2. Overall, our data demonstrated that PM_2.5 led to pulmonary injury in a time-dependent manner via upregulation of proinflammatory and fibrosis-related genes, and activation of the DNA damage response. Our findings provided a novel perspective on the pathophysiology of respiratory diseases caused by airborne pollution.

DNA damage; DNA repair; PM2.5; lung fibrosis; lung inflammation.