Table 3.
Ki67 Cell Cycle Analysis
| Group | Ki67-Positive Nuclei per Field | ||||
|---|---|---|---|---|---|
| Intraglomerular | Podocyte | PEC | Periglomerular/Interstitial | Tubular | |
| TG.1K.ALD (FSGS) | 10.3±1.7a | 0.01±0.1 | 2.8±0.7a | 8.2±2.2a | 4.0±1.1a |
| TG.2K.ALD | 6.4±0.9a | 0.1±0.1 | 0.9±0.4 | 3.2±0.5 | 2.0±0.4 |
| TG.1K.CRD | 1.9±1.2 | 0.0±0.0 | 0.6±0.3 | 1.7±0.9 | 0.7±0.4 |
| TG.1K.ALD.Rapa | 2.0±1.2 | 0.0±0.0 | 0.4±0.2 | 2.3±0.8 | 1.1±0.7 |
| TG.1K.ALD.ACEi | 2.8±0.6 | 0.0±0.0 | 0.7±0.3 | 2.7±1.0 | 1.3±0.5 |
| WT.2K.ALD | 4.5±1.0a | 0.0±0.0 | 0.7±0.4 | 3.2±0.8 | 2.5±0.9 |
| WT.1K.ALD | 6.7±1.0b | 0.0±0.0 | 0.6±0.3 | 2.6±0.2 | 2.8±1.1 |
Ki67-positive cell nuclei in different kidney compartments in nephrectomized (1K) or sham-nephrectomized (2K) TG and WT rat groups under different conditions. Group descriptors (n=5–7) are shown at left. Statistical indicators using ANOVA with Bonferroni adjustment compare each group with the reduced calorie intake group (TG.1K.CRD). All rats were the same age, weight, and sex at start of study 3 weeks before analysis. There were no changes in podocyte Ki67-positive nuclei in any group, and in a parallel study no Ki67 cell nuclei were identified that were also WT1-positive (data not shown) and no binucleate WT1-positive cells were identified, indicating that cells designated as podocytes on the basis of their anatomic localization were probably PECs. In the TG.1K.ALD group that developed FSGS (top row), Ki67-positive nuclei were statistically increased in all other kidney compartments. In the Sham nephrectomized TG group (TG.2K.ALD) and WT nephrectomized and sham-nephrectomized groups only intraglomerular Ki67-positive cells were significantly increased above the reduced calorie intake (TG.1K.CRD) group, but these three groups also had significantly fewer intraglomerular Ki67-positive cells than the TG.1K.ALD (FSGS) group (P<0.01). Prevention of FSGS development by three different methods (CRD, Rapamycin, or ACE inhibition) all showed the similar Ki67 data demonstrating low cell division in all kidney compartments indicating that cell division rate was similarly slowed by all three strategies. These data are consistent with the concept that growth represented by Ki67-positive cells was required for FSGS development. If cell division/growth was prevented (by calorie reduction, rapamycin, or ACE inhibitor) or was not sufficiently rapid (sham-nephrectomy), or the susceptibility transgene was absent (WT rats), FSGS did not occur within the 3-week time frame of study. Statistical comparisons by ANOVA with Bonferroni correction. Data are mean±SD. TG, Fischer344 TG rats; 1K/2K, nephrectomized/sham-nephrectomized; ALD, ad libitum diet; CRD, 40% calorie reduced diet; rapa, rapamycin-treated; ACEi, treated with the angiotensin II inhibitor enalapril; WT, wild-type Fischer344 rats.
P<0.01.
P<0.05.