Fig. 5: Tubule-specific knockout of S100a7a mitigates cisplatin nephrotoxicity.

a Schematic illustration of renal tubule-specific S100a7a knockout (S100a7a^Ksp-KO) mice generation by cross-breeding Ksp-Cre mice with S100a7a^flox/flox mice. The illustration elements were created in BioRender. Chen, Q. (2025) https://BioRender.com/k19218v. b Representative immunofluorescence images of S100A7A (red) and LTL (green) from WT and S100a7a^Ksp-KO mice on day 3 after cisplatin treatment. Scale bars, 100 μm. c Serum creatinine levels in S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment (n = 10 biological replicates). d,e Representative images of H&E staining (d) and corresponding renal tubular injury scoring (e) of renal sections from S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment (n = 10 biological replicates). Scale bars, 100 μm. f RT-qPCR analysis of Tnf and Il6 mRNA expression from S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment (n = 10 biological replicates). g,h Western blot analysis (g) and densitometric quantification (h) of NGAL, cleaved-caspase-3, caspase-3, and S100A7A protein levels in renal tissues from S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment (n = 10 biological replicates). i Representative images of TUNEL staining of renal sections from S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment. Boxed areas were shown at higher magnification in the lower panel. Scale bars, 200 μm. j Quantitative analysis of TUNEL-positive tubules from experiments in panel (i) (n = 10 biological replicates). k–m Representative immunohistochemistry staining (k) of F4/80 and MPO in renal sections from S100a7a^Ksp-KO mice and their WT littermates on day 3 after cisplatin treatment. Quantitative analysis of F4/80-positive cells (l) and MPO-positive cells (m) (n = 10 biological replicates). Data were expressed as means ± SEM. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001 versus WT cisplatin mice. P-values were determined by one-way ANOVA (with LSD or Games-Howell post hoc tests) in (c, f, h, j, l, m). P values were determined by a two-tailed nonparametric test (with Wilcoxon test) in (e). Source data are provided as a Source Data file.