Apoptosis in podocytes induced by TGF-β and Smad7
J. Clin. Invest. Mario Schiffer, et al. 108:807 doi:10.1172/JCI12367 [
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Figure 2(
a–
f) PAS staining and anti-Smad7 immunoperoxidase labeling of renal cortex sections of WT (
a and
d) and TG mice (
b and
e) at 2 weeks (TG 2 wk) (
a–
c) and 5 weeks (TG 5 wk) (
d–
f) of age. Absence of Smad7 immunoperoxidase labeling in the presence of blocking peptide in 2-week-old (
c) and 5-week-old (
f) TG mice as control for specificity of staining. Dotted arrows depict Smad7-negative podocytes and stars denote Smad7-positive mesangial areas (
a and
d). Arrows indicate Smad7-positive podocytes with representative features of damage, including pseudocyst formation and partial or complete detachment from basement membrane (
b and
e). Arrowhead shows synechiae of basement membrane and Bowman’s capsule (
e). (
g) Histogram shows average numbers of podocytes (filled bars) and Smad7-positive podocytes (hatched bars) per central glomerular section. Bars represent average ± SEM numbers of cells per glomerular section determined from 180 glomeruli (30 per mouse) in TGF-β1 TG mice at 2 weeks and at 5 weeks of age, respectively, and 240 glomeruli (30 per mouse) in the WT. Results of
t test: *Podocyte counts in WT vs. TG 2 wk,
P < 0.001;
+Smad7-positive podocyte counts in WT vs. TG 2 wk; **podocyte counts in WT vs. TG 5 wk,
P < 0.001;
++Smad7-positive podocyte counts in WT vs. TG 5 wk,
P < 0.001. (
h) Histogram shows numbers of podocytes with criteria of injury (filled bars) and Smad7-positive injured podocytes (hatched bars). Annotations are as described in
g. (
i) Histogram shows glomerular surface area (filled bars) and mesangial surface area (hatched bars) per glomerular section in arbitrary units (annotations as in
g). Line graph indicates ratio of Smad7-positive mesangial area to total mesangial area (see Methods for definitions).