Figure 7

Proliferation and apoptosis in Cd79a-Tsc1 knockout (KO) kidneys. (a) Immunohistochemistry for proliferating cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Cd79a-Tsc1 KO kidneys were stained across developmental timepoints from postnatal week 1 to 19. In Cd79a-Tsc1 KO tubules at 4 weeks of age, PCNA-positive cells occasionally existed in both the cyst-lining (arrows) and non-cystic tubules (double arrows), while apoptosis was rarely observed. At 9 weeks, the number of PCNA-positive cells increased in the cyst-lining epithelia. In concordance with the increasing proliferation, apoptosis was more frequently observed in the cyst lining and interstitium. At later stages (12 weeks), apoptosis was seen focally in the cyst walls comprising multilayered, actively proliferating epithelial cells (dashed arrows) as well as in the cell debris that was exfoliated into the lumen (arrowheads). (b) Quantitative analysis. The frequencies of PCNA- and TUNEL-positive cells in tubules were greater in Cd79a-Tsc1 KO kidneys than in age-matched controls. After postnatal day 14, the enhanced proliferation in Cd79a-Tsc1 KO tubules became clearly discernible from controls (P < 0.0001). In parallel with the accelerated proliferation, apoptotic cells gradually increased with age and reached a significant difference compared to controls after 9 weeks. Data represent mean ± SEM and were statistically analyzed by two-way ANOVA. . *P < 0.05, **P < 0.01, and ****P < 0.0001.