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http://www.kidney-international.org
& 2006 International Society of Nephrology
Department of Pathology, Vanderbilt University Medical Center, Nashville, Tennessee, USA; 2Department of Nephrology, Huashan
Hospital, Shanghai Medical School, Fudan University, Shanghai, China and 3Department of Pediatrics, Vanderbilt University Medical
Center, Nashville, Tennessee, USA
original article
200
150
100
P0
P6
CONT
50
0
W0
W4
Time
W8
a
24 h urine protein (mg/24 h)
900
800
700
600
500
400
300
200
100
0
P0
P6
CONT
W0
b
GFR (ml/min per 100 g BW)
RESULTS
Body and renal functional changes
W4
W8
W12
P = NS
0.12
0.10
0.08
P < 0.05
P0
P6
CONT
0.06
0.04
0.02
0.00
original article
P0
P6
CONT
PPAR
P = NS
Sclerosis index (SI)
3.50
WT1
PPAR+WT1
P < 0.05
Normal
CONT
P0
P6
3.00
2.50
2.00
1.50
P0
P6
CONT
1.00
0.50
0.00
original article
WT1-positive cell/glomerulus
PCNA-positive/apoptotic cells
P < 0.05
P < 0.05
2.0
1.5
P0
P6
CONT
1.0
P0
P6
CONT
TIMP-1
TGF-
0.5
PAI-1
0.0
GAPDH
P = NS
25.0
20.0
15.0
P0
P6
CONT
P = NS
1.2
P = NS
P = NS
P = NS
P = NS
P < 0.05
P < 0.05
1.0
P0
P6
CONT
0.8
10.0
0.6
5.0
0.4
0.0
0.2
ED-positive cell/glomerulus
P < 0.05
14.0
12.0
10.0
P0
P6
CONT
P < 0.05
8.0
0.0
P0
TGF-
TIMP-1
P6
PAI-1
CONT
6.0
4.0
2.0
0.0
original article
a
P0
P6
CONT
P = NS
2.0
P < 0.05
1.8
P0
P6
CONT
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
P0
P6
CONT
b
P0
P6
CONT
VEGF
-Actin
Flk-1
P < 0.05
-Actin
3.0
P = NS
P = NS
P0
P6
CONT
VEGF
Flk-1
VEGF-positive
cells/glomerulus
2.5
2.0
1.5
1.0
0.5
0.0
P = NS
P = NS
2.5
2.0
P < 0.05
P0
P6
CONT
1.5
1.0
0.5
0.0
Figure 9 | VEGF and Flk-1 expression. (a) There was no significant change in any group in expression of VEGF or Flk-1 from whole kidney
cortex homogenates (Western, protein expressed relative to b-actin). (b) VEGF was expressed on tubular, endothelial cells, macrophages, and
podocytes. In glomeruli, both pre- and post-treatment PPARg agonist rats had more VEGF-positive cells compared to control (anti-VEGF
antibody; original magnification 200).
1760
original article
1.4
1.2
1.0
P0
P6
CONT
P < 0.05
0.8
0.6
0.4
0.2
0.0
Table 1 | Summary of effects of early vs delayed treatment with PPARc agonist in PAN nephropathy
Urinary protein
GFR
SI
WT-1
ED1
PCNA+/apoptosis cells
PAI-1
CD31
VEGF
Aglp4
CONT
Pretreatment
Delayed treatment
361.0783.0
0.02470.005
2.9470.13
0.770.11
11.570.7
13.3976.06
0.4070.05
1.0670.13
1.7070.26
1.0770.16
352.2758.1
0.03270.004
2.6270.09
1.670.20*
7.371.02*
5.9572.12
0.2170.02*
1.3970.09
2.5170.28*
0.1870.05*
377.0766.8
0.08270.026*
2.3370.09*
1.270.18*
5.070.53*
5.6172.25
0.2670.03*
1.6770.09*
2.5270.25*
0.3970.09*
Aglp4, angiopoietin-like protein 4; PAI-1, plasminogen activator inhibitor-1; PCNA, proliferating cell nuclear antigen; SI, sclerosis index; VEGF, vascular endothelial-derived
growth factor; WT-1, Wilms tumor 1.
Pretreatment did not protect against PAN-induced injury, whereas delayed PPARg agonist did. The delayed treatment group had more CD31 and Aglp4 expression,
restoration towards normal WT-1, and increased CD31, and less macrophages than pretreatment.
*Po0.05 vs control.
1761
original article
original article
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