Water‐soluble fraction of particulate matter <2.5 μm promoted lung epithelia cells apoptosis by regulating the expression of caveolin‐1 and Krüppel‐like factor 5

Abstract

Ambient fine particulate matter of <2.5 μm (PM2.5) has been linked to morbidity and mortality from respiratory and cardiovascular diseases. Lung epithelial cells bear the brunt of PM2.5 exposure. In the present study, we found that exposure of A549 cells to the water‐soluble fraction of PM2.5 (WS‐PM2.5) promoted the expression and internalization of caveolin‐1. Caveolin‐1 knockdown restrained the endocytosis of WS‐PM2.5. In addition, WS‐PM2.5 accumulation in the cells induced the phosphorylation of serine/threonine protein kinase B (AKT) and nuclear factor κ‐light‐chain enhancer of activated B cells (NFκB), as well as the expression of Krüppel‐like factor 5 (KLF5). Inhibiting activation of AKT and NFκB also partly reduced WS‐PM2.5 concentration in cells, but KLF5 knockdown did not affect the intracellular accumulation of WS‐PM2.5. KLF5 knockdown suppressed cytochrome P450 family 1 subfamily A member 1 (CYP1A1) expression and activated caspase 3. Luciferase reporter assay and chromatin immunoprecipitation assay showed that KLF5 positively regulated the transcription of KLF5. These results suggested that caveolin‐1 was required for the endocytosis of WS‐PM2.5. Intracellular accumulation of WS‐PM2.5 activated AKT and NFκB, which facilitated WS‐PM2.5 endocytosis. WS‐PM2.5 accumulation also induced KLF5 expression, increasing the transcriptional expression of CYP1A1, which contributed to activate caspase 3.

Lentinan Attenuated the PM2.5 Exposure-Induced Inflammatory Response, Epithelial–Mesenchymal Transition and Migration by Inhibiting the PVT1/miR-199a-5p/caveolin1 Pathway in Lung Cancer

“…Caveolin 1 involves in the EMT in lung cancer (Garnett, 2016;Shi et al, 2020). A report revealed that caveolin-1 regulated the PM2.5-induced endocytosis in lung cancer (Wei et al, 2020). Several studies demonstrated that caveolin-1 was regulated by miR-199a (Zhang et al, 2015;Zhong et al, 2020).…”