Effect of genetic deletion of Gsdmd on mice fed an oxalate rich-diet

The role of pyroptosis, an inflammatory form of cell death involving the formation of Gasdermin-D (GSDMD) pores, in chronic oxalate nephropathy remains unknown. We report genetic deletion of Gsdmd exacerbated oxalate nephropathy in mice in association with accelerated necroptosis.Our transcriptional analysis using kidneys from mice fed an oxalate-rich diet or control diet revealed significant changes in the gene sets related to leukocyte migration, chemokine pathways, mitochondrial dysfunction, and complement pathways between Gsdmd KO and WT mice. These differences may be attributed to variations in the substances released during cell death. Overall design: To investigate potential therapeutic targets in chronic oxalate nephropathy, we fed WT mice an oxalate-rich, calcium-depleted diet to induce progressive oxalate nephropathy, or control diet, and sacrificed them on day 20. We then performed gene expression profiling analysis using data obtained from RNA-seq of kidneys from mice fed an oxalate rich-diet or fed a control food. Furthermore, to investigate the effect of genetic Gsdmd deletion on chronic oxalate nephropathy, we fed Gsdmd kcockout mice an oxalate rich-diet and conducted gene expression profiling analysis using data obtained from RNA-seq of kidneys from these mice.