OBJECTIVE
To improve the understanding of the pathogenesis of lupus nephritis (LN) by studying the relationship between apoptosis and proliferation in children with LN.
METHODS
Thirty-one children (23 girls, 8 boys, aged 6-16 years) with biopsy-proven LN (21 type IV, 6 type V, 2 type II and 2 type III) and nine controls were included in the study. Apoptosis was detected by in situ nick-end labeling techniques (TUNEL) in renal biopsy samples. Proliferation was shown by PCNA detection. Immunohistochemistry was employed to detect the expressions of PCNA, PDCD5 and Caspase-3. The images of glomeruli (G) and renal tubuli (T) were selected randomly on each biopsy sample, respectively, and transferred into computer by SECOM video camera. The quantity of PDCD5 and Caspase-3 expressions were evaluated according to the average intensity of PDCD5 and Caspase-3.
RESULTS
- Compared to control group, the patients with LN had increased apoptotic cells (G: 0.14 +/- 0.09 vs. 0.86 +/- 0.26; T: 0.16 +/- 0.07 vs. 1.16 +/- 0.42; P < 0.01) and increased PCNA positive cells (G: 0.47 +/- 0.25 vs. 8.45 +/- 2.83; T: 1.32 +/- 0.15 vs. 13.73 +/- 3.54; P < 0.01) in glomeruli and renal tubuli. The high ratios of PCNA/apoptosis (P/A) were observed in glomeruli (3.37 +/- 1.93 vs. 10.01 +/- 2.96, P < 0.01) and tubuli (8.94 +/- 1.79 vs. 12.81 +/- 3.91, P < 0.05) in LN group. 2. There was no difference in expression of PDCD5 in glomeruli between LN children and controls (0.09 +/- 0.05 vs. 0.08 +/- 0.02, P > 0.05). The expression of PDCD5 in renal tubuli decreased significantly in LN children compared with controls (0.13 +/- 0.05 vs. 0.21 +/- 0.07, P < 0.01). 3. The expression of Caspase-3 in children with LN increased significantly in glomeruli and tubuli compared with that in controls (0.22 +/- 0.07 vs. 0.05 +/- 0.02; 0.08 +/- 0.03 vs. 0.05 +/- 0.01; P < 0.01). 4. The number of glomerular apoptotic cells showed a positive correlation with the expression of Caspase-3 (r = 0.718, P < 0.01), but no correlation with the expression of PDCD5 in all cases (r = 0.054, P > 0.05). The intensity of PDCD5 expression in glomeruli and renal tubuli showed no correlation with that of Caspase-3 expression in all cases (r = 0.061, P > 0.05, r = 0.049, P > 0.05). Stepwise multiple regression revealed that the number of apoptotic cells in renal tubuli correlated negatively with the intensity of PDCD5 expression, whereas correlated positively with intensity of Caspase-3 expression in all cases.
CONCLUSIONS
- Although the number of apoptotic cells in the kidney of LN was more than that in the kidney of control group, the apoptosis in the kidney of LN was relative insufficient compared with the proliferation. 2. Caspase-3 was involved in the apoptosis of glomeruli and renal tubuli of LN. 3. It was unclear if PDCD5 participated in the apoptosis of glomeruli of LN. While PDCD5 might participate the apoptosis of renal tubuli in LN.
