Inhibition of NLRP3 alleviates calcium oxalate crystal-induced renal fibrosis and crystal adhesion

Kidney stones are gaining attention as one of the most common urological diseases. In this study, we first found that the levels of NLRP3, CASP1, and ASC, which make up the inflammatory vesicle complex, as well as the level of IL-1B secreted by the inflammatory vesicle complex, were elevated, as shown by RNA-seq analysis. We then examined NLRP3 expression via immunohistochemistry, immunofluorescence, qPCR, and Western blotting in human samples, COM-stimulated HK2 cells, and a model of calcium oxalate crystal deposition via intraperitoneal injection. We then constructed systemic NLRP3 knockout mice and found via RNA-seq that calcium oxalate crystal-induced renal fibrosis and crystal adhesion may be attenuated after the knockout of NLRP3. We further substantiated these findings by knocking down NLRP3 both in vitro and in NLRP3-knockout mice. Consistently, we observed more pronounced calcium oxalate crystal-induced renal fibrosis and enhanced crystal adhesion upon overexpression of NLRP3 in vitro and in vivo. Ultimately, we utilized the NLRP3 inhibitor MCC950 to support the potential of NLRP3 as a therapeutic target. Our study suggested that NLRP3 plays an important role in kidney stones by alleviating CaOx crystal-induced renal fibrosis and crystal adhesion.