Fig. 4: GSDME depletion exacerbates cisplatin nephrotoxicity by upregulating S100A7A expression in PTCs.

a Venn diagram illustrating the overlap of upregulated DEGs among three comparisons: KO ctrl vs. WT ctrl, WT cisplatin vs. WT ctrl, and KO cisplatin vs. WT cisplatin. b, c Western blot (b) and densitometric quantification (c) of S100A7A in primary PTCs (n = 4 biological replicates). d, e Western blot (e) and densitometric quantification (d) of S100A7A in renal tissues from cisplatin-treated WT and Gsdme-KO mice (n = 12 biological replicates). f S100A7A concentrations in the culture medium from primary PTCs (n = 3 biological replicates). g Gene expression z-scores of S100a7a in PTCs from WT cisplatin kidneys in scRNA-seq data. h, i Representative S100A7A immunohistochemistry staining (h) and H-score analysis (i) in cisplatin-treated WT and Gsdme-KO mice (n = 12 biological replicates). j Survival analysis of cisplatin-treated WT and Gsdme-KO mice injected with lenti-NC or lenti-S100a7a-shRNA. (k) Serum creatinine levels of cisplatin-treated WT and Gsdme-KO mice injected with lenti-NC or lenti-S100a7a-shRNA (n = 12 biological replicates). l, m Representative H&E-stained (l) and histopathology scoring (m) of cisplatin-treated WT and Gsdme-KO mice injected with lenti-NC or lenti-S100a7a-shRNA (n = 12 biological replicates). n RT-qPCR analysis of Tnf and Il6 from cisplatin-treated WT and Gsdme-KO mice injected with lenti-NC or lenti-S100a7a-shRNA (n = 12 biological replicates). o–r Representative F4/80 (o) and MPO (p) immunohistochemistry staining of cisplatin-treated WT and Gsdme-KO mice injected with lenti-NC or lenti-S100a7a-shRNA. Quantitative analysis of F4/80 (q) and MPO positive cells (r) (n = 12 biological replicates). Data were expressed as means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 versus WT cisplatin group. &P < 0.05, & &P < 0.01, & & &P < 0.001 versus WT ctrl group. #P < 0.05, ##P < 0.01, ###P < 0.001 versus Gsdme-KO mice treated with cisplatin and lenti-S100a7a-RNA. P-values were determined by one-way ANOVA (with LSD or Games-Howell post hoc tests) in (c, d, f, i, k, m, n, q, r). P-values were determined by a two-tailed nonparametric test (with Wilcoxon test) in (m). All scale bars, 100 μm. Source data are provided as a Source Data file.