Urban particulate matter induces NLRP3/NLRP6 inflammasomes, autophagy, senescence and fibrotic responses by increasing CSF2 signaling in kidney cells

Urban traffic represents a significant source of fine particulate matter (PM), which significantly contributes to ambient air pollution. A growing body of evidence indicates that exposure to PM can adversely affect kidney function, although the detailed molecular mechanisms remain incompletely understood. In this study, we employed RNA sequencing to investigate transcriptomic alterations in renal epithelial cells following PM exposure, aiming to identify key signaling pathways and regulatory factors underlying these cellular responses. Our transcriptomic profiling revealed robust activation of stress- and inflammation-associated pathways, with CSF2 emerging as the most prominently upregulated regulator. Exposure to PM induced increased expression of CSF2, IRF4 and phosphorylated STAT3, collectively promoting processes such as fibrosis, inflammasome activation, autophagy, and cellular senescence. Notably, the targeted silencing of CSF2 significantly reduced these PM-induced effects, underscoring its central role in orchestrating these biological responses. In addition, PM exposure stimulated the release of extracellular vesicles (EVs), suggesting that PM may also influence intercellular communication within the renal microenvironment. In a rat model simulating long-term urban PM exposure, we observed clear signs of renal dysfunction and tubular injury, accompanied by elevated CSF2 levels and enhanced expression of markers related to fibrosis, autophagy, cellular senescence and inflammasome activation. These findings highlight CSF2 as a critical mediator linking PM exposure to kidney injury, providing a potential target for therapeutic intervention.