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

Figure 7. Pharmacological inhibition of NLRP3 reduces inflammasome signaling and improves kidney disease in G2APOL1 mice.

Figure 7

(A) Experimental design: G2APOL1 mice were placed on doxycycline diet with or without 30.8 mg/kg (low), 92.4 mg/kg (medium), or 308 mg/kg (high) MCC950 for 3 weeks. (B) Relative APOL1 transcript levels in whole kidney, n = 4. (C) ACR at 1 week on doxycycline, n = 4. *P < 0.05 vs. G2APOL1 sham. (D) BUN, (E) serum creatinine, and (F) relative transcript levels of Nlrp3, Casp1, Il1b, and Il6 in control (n = 3), G2APOL1 (n = 4), low (n = 4), medium (n = 4), and high dose MCC950 (n = 4). #P < 0.05, ##P < 0.01, ###P < 0.001 vs. control; *P < 0.05 vs. G2APOL1. (G) Representative PAS-stained and (H) Sirius red–stained kidney section. Scale bars: 30 μm. (I) Quantification of Sirius red–positive area, n = 4 mice. *P < 0.05, **P < 0.01 vs. G2APOL1. (J) Percentage of attenuated epithelium with casts in G2APOL1 (n = 4), low (n = 4), medium (n = 4), and high dose MCC950 (n = 4). *P < 0.05, ***P < 0.001 vs. G2APOL1. (K) Relative mRNA levels of Col3a1, Fn1, and Vim, and (L) Ccl2, Tnfa, and Cxcl2 were evaluated in the kidneys of control (n = 3), G2APOL1 (n = 4), medium (n = 4), and high dose MCC950 (n = 4). ###P < 0.001 vs. control; **P < 0.01, ***P < 0.001 vs. G2APOL1 sham. (M) ACR in G2APOL1 mice treated with high dose MCC950 at baseline, 1, 2, 6, and 10 days on doxycycline diet (n = 6). *P < 0.05 vs. G2APOL1. (N) Serum creatinine levels and (O) relative transcript levels of Nlrp3, Casp1, Il1b, and Il6 in control, G2APOL1, and high dose MCC950 (n = 6). **P < 0.01, ***P < 0.001 vs. control; #P < 0.05, ##P < 0.01 vs. indicated group. Significance was determined by 1-way ANOVA and SNK post hoc test. Data are expressed as the mean ± SEM.