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. 2021 Oct 15;131(20):e136329. doi: 10.1172/JCI136329

Figure 6. Pharmacological inhibition of GSDMD and STING improves kidney disease in G2APOL1 mice.

Figure 6

(A) Experimental design: G2APOL1 mice were placed on doxycycline diet and treated with GSDMD inhibitor (disulfiram) or STING inhibitor (C176) or sham for 10 days. (B) Relative APOL1 transcript levels in whole-kidney tissue of G2APOL1 sham (only doxycycline diet; n = 6), disulfiram (n = 6), and C176 (n = 6). (C) Albuminuria (ACR) levels of control (n = 6), G2APOL1 (n = 6), disulfiram-treated (n = 6), and C176-treated (n = 6) G2APOL1 mice. ***P < 0.001 vs. control; #P < 0.05 vs. G2APOL1. (D) Serum creatinine levels of control (n = 6), G2APOL1 (n = 6), disulfiram-treated (n = 6), and C176-treated (n = 6) G2APOL1 mice. ***P < 0.001 vs. control; #P < 0.05, ##P < 0.01 vs. G2APOL1. (E) BUN levels of control (n = 6), G2APOL1 (n = 6), disulfiram-treated (n = 6), and C176-treated (n = 6) G2APOL1 mice. ***P < 0.001 vs. control; #P < 0.05, ##P < 0.01 vs. G2APOL1. (F) PAS-stained and Sirius red–stained kidney sections of control, G2APOL1, disulfiram-, and C176-treated G2APOL1 mice. Scale bars: 30 μm. (G) Quantification of Sirius red–positive area of control, G2APOL1, disulfiram-, and C176-treated G2APOL1 mice. n = 6 mice per group. ***P < 0.001 vs. control; ###P < 0.001 vs. indicated group. (H) Relative mRNA levels of profibrotic genes Col1a1, Col3a1, Fn1, and Vim; and markers of inflammation Ccl2, Tnfa, and Cxcl2 were evaluated in the kidneys of control, G2APOL1, disulfiram-, and C176-treated G2APOL1 mice. n = 6 mice. **P < 0.01, ***P < 0.001 vs. control; #P < 0.05, ##P < 0.05, ###P < 0.001 vs. indicated group. Significance was determined by 1-way ANOVA and SNK post hoc test. Data are expressed as the mean ± SEM.