Atmospheric fine particulate matter (PM2.5) induces pulmonary fibrosis by regulating different cell fates via autophagy

The presence of respiratory diseases demonstrates a positive correlation with atmospheric fine particulate matter (PM_2.5) exposure. The respiratory system is the main target organ affected by PM_2.5, and exposure to PM_2.5 elevates the likelihood of developing pulmonary fibrosis (PF). In this study, lung epithelial cell (BEAS-2B) and fibroblast (NIH-3T3) were used as in vitro exposure models to explore the mechanisms of PF. PM_2.5 exposure caused mitochondrial damage in BEAS-2B cells and increased a fibrotic phenotype in NIH-3T3 cells. Epithelial cells and fibroblasts have different fates after PM_2.5 exposure due to their different sensitivities to trigger Autophagy. Exposure to PM_2.5 inhibits Mitophagy in BEAS-2B cells, which hinders the removal of damaged mitochondria and triggers cell death. In this process, the nuclear retention of the mitophagy-related protein Parkin prevents it from being recruited to mitochondria, resulting in Mitophagy inhibition. In contrast, fibroblasts exhibit increased levels of Autophagy, which may isolate PM_2.5 and cause abnormal fibroblast proliferation and migration. Fibrotic phenotypes such as collagen deposition and increased α-actin also appear in fibroblasts. Our results identify PM_2.5 as a trigger of PF and delineate the molecular mechanism of Autophagy in PM_2.5 induced PF, which provides new insights into the pulmonary injury.

Autophagy; Mitophagy; PM(2.5); Parkin; Pulmonary fibrosis.