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. 2016 Oct 20;1(17):e87877. doi: 10.1172/jci.insight.87877

Figure 5. Pharmacological inhibition of MDM2 in uninephrectomized Leprdb–/– (db/db) mice fed with high-fat diet.

Figure 5

(A) Survival in Nutlin-3a–treated db/db mice (37.5% at the end of the treatment) compared with that of vehicle-treated db/db mice (57%, P = 0.2, log-rank test). (B) Body weight monitoring along the treatment. Both groups lost weight during the treatment, though Nutlin-3a–treated mice had a lower body weight compared with vehicle-treated mice. (C) Blood urea nitrogen (BUN) levels over the treatment increased in both groups, being higher in Nutlin-3a–treated mice than in vehicle-treated mice. *P = 0.0039, t test, n = 7/group. (D) Immunofluorescence (IF) image of control mouse in upper panel and of Nutlin-3a–treated mouse in lower panel. Magnification, ×60. (E) IF quantification of number of podocytes. Nutlin-3a–treated displayed a lower number of podocytes (6.50 ± 0.14) than vehicle-treated mice (5.84 ± 0.54). *P = 0.0139, Wilcoxon rank sum test. db/db DMSO, n = 4; db/db Nutlin-3a, n = 6. (F) Representative photomicrograph of TP53 staining in the wild-type and db/db mice. Nutlin-3a treatment in db/db mice causes upregulation and nuclear shift of TP53 in renal cells. Representative from n = 5 for each group except wild type treated with Nutlin-3a (n = 4). Magnification, ×200. Error bars in B represent SE. For box-and-whisker plots in C and E, the horizontal line in each box represents the median. The whiskers extend to 1.5 × (third quartile – first quartile).