Differential Lung Proteome Profiles Upon Pulmonary Exposure to Traffic-related Particulate Matter

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> Exposure to particulate matter (PM) pollution has direct impacts on the respiratory organs, yet the molecular alterations underlying PM-induced pulmonary injury remain unclear. In this study, we investigated the effect of PM on lung tissues from our previously reported rat model with whole-body exposure to traffic-related PM<jats:sub>1</jats:sub> pollutants and compared it with rats exposed to high-efficiency particulate air-filtered gaseous pollutants and clean air control for 3 and 6 months. Lung function and histological examinations as well as quantitative proteomics analysis and functional validation were performed. <jats:bold>Results: </jats:bold>The rats in 6-month PM<jats:sub>1-</jats:sub>exposed group showed significant decline in lung function by decreased forced expiratory flow and forced expiratory volume, but the histological analysis revealed an earlier lung damage evidenced by increased congestion and macrophage infiltration in 3-month PM<jats:sub>1</jats:sub>-exposed rat lungs. The lung tissue proteomics analysis identified 2,673 proteins which highlighted dysregulations on proteins involved in oxidative stress, cellular metabolisms, calcium signaling, inflammatory responses, and actin dynamics. The presence of fine particles specifically enhanced the oxidative stress and inflammatory reactions under sub-chronic exposure of traffic-related PM<jats:sub>1</jats:sub> and suppressed the glucose metabolism and actin cytoskeleton signaling which might lead to repair failure and thus lung function decline after chronic exposure of traffic-related PM<jats:sub>1</jats:sub>. A detailed pathogenic mechanism was proposed to depict the temporal and dynamic molecular regulations associated with PM<jats:sub>1</jats:sub>-induced lung injury.<jats:bold>Conclusion:</jats:bold> Our study explored the earlier lung injury prior to lung function decline and proposed several proteins as potential molecular features for traffic-related PM<jats:sub>1</jats:sub>-induced lung injury.</jats:p>