Figure 5.
Integrin-αvβ3 antagonism dose-dependently modulates dNP. (A) Scheme showing the experimental approach and dosing of the integrin-αvβ3 antagonist Cyclo-RGDfv in wild-type mice with STZ-induced persistent hyperglycemia (DM). (B) Dot plot summarizing urine albumin levels (albumin-creatinine ratio) in control (C) and diabetic (DM) mice; diabetic control mice received PBS. (C) Representative images of glomeruli (top; PAS staining of paraffin-fixed sections; scale bar, 5 μm) and the glomerular filtration barrier (bottom, transmission electron microscopy; scale bar, 0.2 μm) and dot plots summarizing the data for (D) the FMA, (E) the width of the GBM (representative of arrows in the far-left image of [C] only), and (F) tight slit pore density, reflecting foot process effacement. (G) Representative immunoblots of RhoA-GTP (21 kDa), total RhoA (21 kDa), and β-actin (42 kDa) from renal tissue lysates from experimental mice and a dot plot summarizing the data. The data shown in the dot plots represent the mean±SEM of at least eight mice (B–F) or five mice (G) per group; each dot represents data from one mouse. *P<0.05, **P<0.01, ***P<0.001. (B and D–F) ANOVA with Tukey-adjusted post hoc comparison; diabetic mice were compared do nondiabetic mice, and diabetic mice treated with Cyclo-RGDfv were compared with diabetic control mice. C, nondiabetic control mice; DM, mice with persistent hyperglycemia after STZ injection.