Fig. 5: Compound 3 prevents APOL1-mediated morphological and histopathological damage of kidney glomeruli.

A, D, G No microscopic findings were present in control-group. B, E, H Glomerulopathy was frequent and severe in vehicle-treated mice, however all glomeruli were not affected. The affected glomerulus on left (B, E, H, black-arrow) was characterized by synechia (B, grey-star) and duplication of parietal epithelium (E, red-bracket), collapsed capillary lumina, mesangial hyalinization) and accumulation of PAS+ve (E) material in the mesangium. The adjacent glomerulus on right (B, E, H, white-arrow) was morphologically normal. Near total loss of nephrin in the affected glomerulus (H, black-arrow), while the adjacent glomerulus (H, white-arrow) has preserved nephrin staining. C, F, I No findings were noted in Compound 3-treated mice. Scale bar is 10 μm for all images. J Quantitative image analysis of nephrin immunolabeling using H-score. H-score (label intensity * % area); weak (+1), moderate (+2) strong (+3). Nephrin H-score data was analyzed by a Kruskal-Wallis test with post-hoc Dunn’s multiple comparison test. Significance was set at p ≤ 0.05. *p ≤ 0.05. p = 0.0231 for Control vs. Vehicle mice. Results presented as arithmetic mean ± SEM with each symbol representing an individual mouse (closed are females, open are males) with n = 11 mice per group. K–M Maximum intensity projection of kidney filtration slit diaphragm in control mice (K), in mice treated with IFNγ and vehicle (L), and in mice treated with IFNγ and Compound 3 (M). Kidneys were immunolabeled for podocin and integrin α3. Images were acquired with 3D-Structured Illumination Microscopy. Scale bar is 1 μm. The depth color scale goes from −2 μm (red) to 2 μm (blue). N The filtration slit density (FSD) of n = 2−3 mice/group. 20 glomeruli per mouse were randomly selected and analyzed. FSD was calculated as the ratio between filtration slit length and surface area. Data were analyzed with One-way ANOVA. The Benjamini-Hochberg procedure was applied post-hoc to control for false discovery rate. Significance was set at p ≤ 0.05. p = 0.0003 for control vs. Vehicle and p = 0.0002 Vehicle vs. Compound 3. Results presented as arithmetic mean ± SEM with each symbol representing an individual mouse. Representative data of n = 2 experiments shown for all panels. Source data are provided as a Source Data file.