PM2.5 induces renal tubular injury by activating NLRP3-mediated pyroptosis

Fine particulate matter (PM_2.5)-related health issues have received increasing attention as a worldwide public health problem, and PM_2.5-related chronic kidney disease (CKD) has been emerging over the years. Limited research has focused on the mechanism of PM_2.5-induced kidney disease. To investigate the impact of PM_2.5 on the kidney and its potential mechanism, we generated a PM_2.5-exposed C57BL/6 mouse model by using Shanghai Meteorological and Environment Animal Exposure System (Shanghai-METAS) for 12 weeks, urine, blood and kidney tissues were collected. The pathological changes and the function of the kidney were measured after PM_2.5 exposure for 12 weeks. Along with glomerular damage, tubular damage was also severe in PM_2.5-induced mice. The results of mRNA-seq indicate that pyroptosis is involved. Pyroptosis is defined as caspase-1-dependent programmed cell death in response to insults. The expression of the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), Caspase-1, gasdermin D (GSDMD) and IL-1β was detected. NLRP3 inflammasome activation and subsequent pyroptosis were observed in PM_2.5-exposed kidney tissues and PM_2.5-exposed Bumpt cells too. At the meantime, the inhibitors of NLRP3 and caspase-1 were applied to the PM_2.5 exposed Bumpt cells. It turned out to have a significant rescue effect of the inhibitors. This study revealed new insights into PM_2.5-induced kidney injury and specific kidney pathological damage, as well as morphological changes, and defined the important role of pyroptosis in PM_2.5-induced kidney dysfunction.