Figure 1

Mammalian TOR pathway blockage triggered dual PI3K-dependent feedback loops stemming from S6K to PI3K/ERK and to PI3K/Akt in PKD. (A) Han:SPRD rats whole kidney lysates western blot analysis and densitometry of PI3K/Akt and PI3K/ERK pathway readouts after 12 weeks everolimus (E) or vehicle (V) treatment (n = 4 per group). **p < 0.01 indicated by brackets. (B) mTOR upon treatment with indicated everolimus concentration for 48 h. (C) Cell viability (MTS, left panel) and DNA synthesis (BrdU, right panel) of Cy/ + renal primary tubular epithelial cells (TEC) after combined application of mTOR (everolimus, E), Akt (UO126, U) and ERK (perifosine, P) inhibitors for 48 h. #p < 0.001 compared to control, except where indicated by brackets. (D) Western blot analysis of mTOR, PI3K/Akt and PI3K/ERK pathways after 48 h combination treatment with the indicated inhibitors in Cy/ + TEC. Graphs are representative of three independent experiments. These are cropped gels and the original gels are presented in Supplementary Fig. 6.