498925.fig.006a
(a)
498925.fig.006b
(b)
498925.fig.006c
(c)
498925.fig.006d
(d)
498925.fig.006e
(e)
498925.fig.006f
(f)
498925.fig.006g
(g)
Figure 6: Podocyte injury in + Unx mice. (a) At the ultrastructural level, KK-a/a controls had normal podocyte foot processes (white arrows) and a smooth, trilaminar glomerular basement membrane. In (b) and + Unx (c) mice, there was podocyte foot process effacement (white arrows) and areas of mild irregular GBM thickening (black arrows). Regions of uneffaced foot processes ((b), inset) were present in both cohorts, and uninephrectomy did not induce discernable differences in the severity of glomerular basement membrane thickening. Podocyte counting was carried out using WT-1 as a specific podocyte marker. The total number of cells per glomerular area (d) was unchanged between any of the groups, but glomerular area was significantly increased in all animals (e). In uninephrectomized mice, the number of WT-1-positive cells per glomerular area was reduced by 28% ( ). The number of podocytes per glomerulus (independent of area) was also decreased in (18% of total cells in KK-a/a, 16% in HF, and 13% in HF Unx (data not shown)) suggesting that loss of podocytes is not simply due to increased glomerular area. (g) qRT-PCR analysis of podocyte-specific genes further supports podocyte loss, revealing statistically significant decreases in nephrin, podocin, and WT-1 RNA expression in HF Unx kidneys.