Molecular Mechanism Of Pulmonary Senescence And Fibrosis Induced By Atmospheric Fine Particles And Their Main Components

Particulate matter 2.5(PM2.5)is a widely known atmospheric pollutant.With the rapid development of China's economy and industry,PM2.5 has become one of the main environmental pollution factors in China.Because of its complex internal components,small unit size and large specific surface area,PM2.5 can cause multiple system,multiple organ dysfunction even pathological changes,which will cause adverse effects on human health life.Recent studies have shown that long-term exposure to PM2.5 could induce a multiple of pulmonary diseases such as acute respiratory distress syndrome(ARDS),chronic obstructive pulmonary disease(COPD)and interstitial pulmonary fibrosis(IPF).Therefore,in order to meet the urgent needs of the public for living environment and health,it is necessary to carry out relevant basic research on the pathophysiological mechanism of PM's health effect at the current situation that the emission sources of air pollution are difficult to be completely solved for the time being.The purpose of our study is to determine the occurrence of effects between PM2.5and senescence or fibrosis,build a micro mechanism bridge between atmospheric fine particle pollution and respiratory health hazards.Meanwhile,it may provide new strategies and basis for early detection,risk assessment,protective treatment and prevention of related diseases.In conclusion,our study started from lung epithelial(A549)cells and discussed the effects of PM2.5 and its main components on lung epithelial(A549)cells.It also expounds two aspects:(1)Our study focused on the effect of PM2.5 on the senescence of pulmonary epithelial(A549)cells,identifying which pathway mediated PM2.5-induced cellular senescence and how to play a protective role against this issue.Our data suggested that PM2.5 induced time-and concentration-dependent increasement in the senescence of pulmonary epithelial cells.Using a inhibitor of c GAS(PF-06928215)and a inhibitor of NF-?B(BAY 11-7082),it was revealed that PM2.5-induced senescence was regulated by inflammatory response,which was closely related to the c GAS/STING/NF-?B pathway activated by DNA damage.Moreover,our study also showed that when A549 cells were exposed to 100 ?g/m L PM2.5 for 48 h,the pretreatment with 20 ?M selenomethionine(Se-Met)for 12 h could inhibit PM2.5-induced inflammatory response and prevent cellular senescence by hindering c GAS/STING/NF-?B pathway.(2)Our study focused on the effect of B[a]P,the main component of PM2.5,on the fibrosis of pulmonary epithelial(A549)cells,identifying whether B[a]P-induced epithelial mesenchymal transformation(EMT)mediates the fibrosis of A549 cells and whether iron is involved in the regulation of this process.Our data suggested that B[a]P induced time-and concentration-dependent increasement in the fibrosis of pulmonary epithelial cells.Further experiments on the occurrence of EMT showed that B[a]P could lead to EMT in A549 cells in a time and concentration dependent manner.At the same time,the content of iron in A549 cells also increased significantly during epithelial mesenchymal transformation.These findings suggest that B[a]P could induce fibrosis in pulmonary epithelial,and this process may be related to EMT and endogenous iron content.