Figure 4.

Uroplakin and tight junction gene expression is downregulated by diabetes via NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)-dependent mechanisms at the 15-wk (overactive detrusor) time point. Urothelia were scraped from excised bladders, and quantitative PCR was used to measure gene expression of uroplakin subunits UP1b and UP2, tight junction components zona occludens 1 and 2 (ZO1 and ZO2, respectively), claudin 4 and 8 (CL4 and CL8, respectively), and the adherens junction component β-catenin (BCAT). A: at 15 wk, UP1b was downregulated in diabetic NLRP3^+/+ mice. B: NLRP3 gene deletion prevented this downregulation in diabetic NLRP3^−/− mice. C: at 15 wk, UP2 was downregulated in diabetic NLRP3^+/+ mice. D: NLRP3 gene deletion prevented downregulation of UP2 in diabetic NLRP3^−/− urothelia. E, G, I, and K: tight junction genes ZO1, ZO2, CL4, and CL8 were expressed significantly less in diabetic NLRP3^+/+ mice. F, H, J, and L: however, gene expression was not significantly downregulated in diabetic NLRP3^−/− mice. M and N: no statistically significant changes in BCAT gene expression were noted at 15 wk. Respective n (animals) per group, per condition = UP1b (8, 7, 12, and 10), UP2 (7, 7, 12, and 10), ZO1 (8, 7, 12, and 10), ZO2 (6, 6, 7, and 6), CL4 (8, 7, 12, and 10), CL8 (6, 6, 7, and 6), and BCAT (8, 6, 12, and 10). *P < 0.05 vs. nondiabetic control mice (Student’s t test).