Figure 7. Pharmacological inhibition of mTOR signaling impairs podocyte hypertrophy and leads to FSGS.
(A) Schematic representation of experimental design. (B) Representative confocal images after indirect immunofluorescence showing pharmacological inhibition of ribosomal protein S6 phosphorylation (p-rp-S6; green) in podocytes (Synaptopodin; SNP in red). (C) Urinary albumin to creatinine ratio (UACR). (D) Periodic acid–Schiff (PAS) histological stainings showing glomerulosclerosis in mTOR-treated mice during induction of podocyte loss. (E) Percentage of pathological glomeruli. (F) Representative confocal images after indirect immunofluorescence showing de novo PEC activation (CD44 upregulation; green) in mice treated with mTOR inhibitors during induction of podocyte loss via diphtheria toxin (DT) administration. (G) Podocyte number. (H) Total podocyte volume per unit of podocyte density (TPV:PD ratio). ****P < 0.0001; ***P < 0.001; **P < 0.01. In C and E, circles and bars represent means and error bars ± SEM. In violin plots, red lines represent medians and blue lines represent IQRs; every gray dot represents 1 glomerulus. Kruskal-Wallis with Dunn’s multiple comparisons tests were used. Scale bars: (B) 30 μm, (D) 60 μm, and (F) 50 μm.