Fig. 7: Tubule-specific knockdown of Gsdme aggravates cisplatin nephrotoxicity.

a Schematic illustration of Ksp-Cre-driven Gsdme knockdown (KD) virus administration in Ksp-Cre mice. The illustration elements were created in BioRender. Chen, Q. (2025) https://BioRender.com/k19218v. b Representative immunofluorescence images of GSDME (red) and LTL (green) in renal sections from Gsdme^Ksp-KD and negative control (NC) mice on day 3 after cisplatin treatment. LTL was used to stain renal proximal tubules. DAPI was used to stain nuclei (blue). c Quantification of GSDME immunofluorescence intensity from experiments in panel (b) (n = 8 biological replicates). d Serum creatinine levels in Gsdme^Ksp-KD and NC mice on day 3 after cisplatin treatment (n = 8 biological replicates). e, f Representative images of H&E staining (e) and corresponding renal tubular injury scoring (f) of renal sections from Gsdme^Ksp-KD and NC mice on day 3 after cisplatin treatment (n = 8 biological replicates). g, h Western blot analysis (g) and densitometric quantification (h) of NGAL, S100A7A, RAGE, and GSDME protein levels in renal tissues from Gsdme^Ksp-KD and NC mice on day 3 after cisplatin treatment (n = 8 biological replicates). i RT-qPCR analysis of Tnf, Ccl2, and Il6 mRNA expression in renal tissues from Gsdme^Ksp-KD and NC mice on day 3 after cisplatin treatment (n = 8 biological replicates). j–m Representative immunochemical staining of F4/80 (j) and MPO (l) in renal sections from Gsdme^Ksp-KD and NC mice on day 3 after cisplatin treatment. Quantitative analysis of F4/80-positive cells (k) and MPO-positive cells (m) (n = 8 biological replicates). Data were expressed as means ± SEM. ^**P < 0.01, ^***P < 0.001 versus Cre⁺ mice treated with cisplatin and NC siRNA. ^###P < 0.001 versus Gsdme^Ksp-KD mice. P-value was determined by Student’s two-tailed t-test in (c). P-values were determined by one-way ANOVA (with LSD or Games-Howell post hoc tests) in (d, h, i, k, m). P values were determined by a two-tailed nonparametric test (with Wilcoxon test) in (f). All scale bars, 100 μm. Source data are provided as a Source Data file.