Figure 7.

β1-Integrin agonist protects animals against proteinuria. (A–C) Pyrintegrin (Pyr) protects mice from LPS-induced proteinuria. (A) Graph showing the ratio of albumin to creatinine in the urine of mice at the indicated time points after LPS administration and treatment with either Pyr (LPS+Pyr) or vehicle alone (LPS+vehicle). Control animals were administered saline alone. Data shown are means±SEMs (n=6–13 per group). *P<0.05. (B) Pyr protects against LPS–induced podocyte FP effacement. Representative electron microscopy image of mouse glomeruli treated with saline alone (control), LPS and vehicle (LPS), or LPS and Pyr (LPS+Pyr). *Effaced FPs in LPS-treated sections. BM, basement membrane. Scale bar, 1 μm. (C) Pyr preserves the level of active β1-integrin expression in the glomeruli. Representative confocal microscopy images of immunofluorescently labeled glomeruli from animals 24 hours after LPS administration. Frozen kidney sections from animals treated with saline alone (control), LPS and vehicle (LPS) or LPS and Pyr (LPS+Pyr) were imaged after staining with 4′,6-diamidino-2-phenylindole (DAPI) and antibodies against total β1 integrin (β1/DAPI), active β1 integrin (active β1), or synaptopodin (synpo). Merged active β1 and synpo channels are also shown (merge column). Scale bar, 25 μm. (D) Pyr protects rats from PAN-induced nephropathy. Graph showing the ratio of albumin to creatinine in the urine of rats at the indicated time points after PAN administration and treatment with either Pyr (PAN+Pyr) or vehicle alone (PAN+vehicle). Data shown are means±SEMs (n=4–6 per group). *P<0.05.