Benzo[a]pyrene induces fibrotic changes and impairs differentiation in lung stem cells

Abstract Human activities have generated air pollution, with extremely small particles (PM 2.5, particulate matter less than 2.5 µm in diameter) and liquid droplets, which become a menace to human health. Among the pollutants, polycyclic aromatic hydrocarbons (PAHs), which enhance the risks of pulmonary dysfunction and cancer development, have been extensively studied. Numerous studies have addressed the effects of PAHs on the respiratory system, whereas the effects on lung stem/progenitor cells remain unknown. Here, we provide evidence that benzo[a]pyrene (BaP), a major toxic PAH, induces fibrotic changes with a loss of α-1,6-fucosylation in CD54+CD157+CD45− cells (lung stem cells). In studies with aryl hydrocarbon receptor (AHR) antagonist, we found that these effects by BaP are independent of the canonical AHR pathway. In addition, these BaP-induced fibrotic changes are reduced by TGF-β antagonist, suggesting an alternative pathway of BaP toxicity is different from other PAH/AHR signaling pathways. Finally, it was observed that BaP impairs the spheroid formation and the podoplanin expression of CD54+CD157+CD45− cells, indicating that BaP suppresses the differentiation of lung stem cells. Taken together, our findings reveal specific BaP-induced injuries in CD54+CD157+CD45− cells.