Fig. 1. HIV-transgenic rats display multiple glomerular phenotypes, disrupted cell cycle regulation and podocyte dedifferentiation and dysregulation.

Panels (a–d) represent renal histology and panels (e–p) represent paraffin kidney sections from wild-type and HIV-Tg rats labeled with antibodies against markers specific for proliferation, podocyte dedifferentiation and dysregulation. (a and b) MT-stained kidney sections from HIV-Tg (b) and wild-type age-matched controls (a). Accumulation of extracellular matrix in HIV-Tg glomeruli was revealed by blue color. (c and d) H&E-stained kidney sections from HIV-Tg (d) and wild-type (c) rats. HIV-Tg rats show signs of podocyte hyperplasia and scarring in a collapsing glomerulus (arrow) compared with wild-type sections (c). (e and f) Labeling for Ki67 revealed cellular proliferation in both the glomeruli (left arrow) and tubules (right arrow) from HIV-Tg sections (f) compared with the wild-type controls (e). (g and h) PCNA-positive cells (arrows) were observed in both wild-type (g) and HIV-Tg (h) kidney sections. (i and j) Normal expression of p27 in quiescent wild-type cells (arrow in i), whereas HIV-Tg glomeruli had decreased expression of p27 (j). (k and l) Kidney sections from both wild-type (k) and HIV-Tg (l) rats were labeled with antibody directed against WT1. The HIV-Tg podocytes exhibited a loss of WT1 expression in the sclerotic glomeruli (l). (m and n) Focal expression of synaptopodin was observed in the sclerotic glomeruli (arrow) (panel n). Arrowheads define the boundary of glomeruli that has lost synaptopodin. Normal synaptopodin expression (m) was seen in wild-type controls. (o and p) Desmin was highly upregulated in dysregulated podocytes from HIV-Tg sections (panel p, arrow), whereas wild-type glomeruli showed no desmin expression (o) (original magnification ×40). H&E, hematoxylin and eosin; HIV-Tg, HIV-transgenic; MT, Mason Trichrome; PCNA, proliferating cell nuclear antigen; WT1, Wilms tumor 1.