FOXP1 deficiency exacerbates cellular senescence in PM2.5-induced renal injury

Exposure to fine particulate matter (PM 2.5 ) represents a critical environmental health threat, with growing evidence linking it to accelerated chronic kidney disease (CKD) progression. However, the underlying mechanism of this toxicity remains poorly understood. This study investigated whether PM 2.5 exposure induces renal tubular cell senescence and explored the molecular basis of this process. We found that PM 2.5 exposure caused kidney injury in mice and upregulated senescence markers in both mice and human kidney proximal tubule epithelial (HK-2) cells. Mechanistically, PM 2.5 downregulated FOXP1 expression, relieving its transcriptional repression of CDKN1A (encoding P21), leading to P21 upregulation and subsequent cell cycle arrest. Overexpressing FOXP1 or treating with quercetin mitigated PM 2.5 -induced senescence in HK-2 cells. Our findings demonstrate that reduced FOXP1 drives cellular senescence in PM 2.5 -induced renal injury and identify quercetin as a potential therapeutic agent that activates FOXP1 and alleviates PM 2.5 nephrotoxicity. • Cellular senescence is a key mechanism of PM 2.5 -induced nephrotoxicity. • PM 2.5 exposure triggers renal tubular cell senescence via downregulating FOXP1. • FOXP1 overexpression suppresses CDKN1A transcription and then alleviates PM 2.5 -induced cellular senescence. • Quercetin activates FOXP1, mitigating PM 2.5 -induced senescence.