Figure 3 | Scientific Reports

Figure 3

From: Dual mTOR/PI3K inhibition limits PI3K-dependent pathways activated upon mTOR inhibition in autosomal dominant polycystic kidney disease

Figure 3

Efficacy of NVP-BEZ235 and sirolimus treatment in Pkd1 conditional knockout mice. (A) Study design scheme. (B) Representative PAS stained kidney sections of NVP-BEZ235-treated, sirolimus-treated and vehicle-treated mice. Quantitative analysis of (C) two kidneys to total body weight ratio (2 K/TBW), (D) BUN, (E) serum creatinine, *p < 0.05, **p < 0.01, #p < 0.001 indicated by brackets (mean ± SD, ANOVA). The number of mice per group is indicated in Supplementary Tables 4 and 5. (F) Whole kidney lysates Western blot analysis of mTOR, PI3K/Akt and PI3K/ERK pathways (G) Schematic representation of the pathways examined in the study. mTOR pathway is abnormally activated in polycystic kidneys (left panel). Treatment with mTOR inhibitor results in a hyperactive PI3K-dependent pathway, increasing the signal toward the PI3K/Akt and PI3K/ERK pathway (middle panel). Dual mTOR/PI3K inhibitor NVP-BEZ235 may provide a therapeutic benefit for ADPKD by abrogating the activation of PI3K/Akt and PI3K/ERK pathways and in turn block the mTOR pathway (right panel). Red denotes activated; blue, inhibited. These are cropped gels and original gels are presented in the Supplementary Fig. 6.

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