Figure 3.
ETA receptor antagonism prevents podocyte loss and preserves podocyte structure in humanized sickle cell mice. Immunohistochemical examination and mRNA expression of markers of podocyte injury of kidneys from genetic control (HbAA) and humanized sickle mice (HbSS) treated with vehicle, the selective ETA antagonist, ambrisentan, or the combined ETA/B antagonist, A-182086, for 10 weeks beginning at 4 weeks of age. (A) Depicts representative WT-1–positive stained sections of glomeruli. Original magnification, ×40 (scale bar=50 μm). (B) Depicts the quantification of (A) represented as the average number of WT-1–positive cells per glomerulus. Podocytes were counted in minimum 20 glomeruli in ten sections per slide. Data are mean±SEM; n=5 in HbAA and HbSS groups. (C) Depicts the relative WT-1 mRNA expression in glomeruli after 10-week treatment protocol. (D) Depicts the relative nephrin mRNA expression in glomeruli after 10-week treatment protocol. (E) Depicts the relative podocin mRNA expression in glomeruli after 10-week treatment protocol. (F) Depicts the relative synaptopodin mRNA expression in glomeruli after 10-week treatment protocol. (G) Depicts representative photomicrographs of transmission electron microscopy sections of glomeruli. Data are mean±SEM; *P<0.05 versus vehicle-treated HbAA; #P<0.05 versus vehicle-treated HbSS; n=5–6 in HbSS and n=6 in vehicle-treated HbAA group.