PM Induces Renal Tubular Injury by Activating NLRP3-mediated Pyroptosis

Fine particulate matter (PM)-related health issues have received increasing attention as a worldwide public health problem, and PM-related chronic kidney disease (CKD) has been emerging over the years. Limited research has focused on the mechanism of PM-induced kidney disease. To investigate the impact of PM on the kidney and its potential mechanism, we generated a PM-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 exposure for 12 weeks. Along with glomerular damage, tubular damage was also severe in PM-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-exposed kidney tissues and PM-exposed Bumpt cells too. At the meantime, the inhibitors of NLRP3 and caspase-1 were applied to the PM exposed Bumpt cells. It turned out to have a significant rescue effect of the inhibitors. This study revealed new insights into PM-induced kidney injury and specific kidney pathological damage, as well as morphological changes, and defined the important role of pyroptosis in PM-induced kidney dysfunction.