Cell proliferation and apoptosis of the glomerular epithelial cells in rats with puromycin aminonucleoside nephrosis.

Injury and repair of the glomerular epithelial cells (GECs) play an important role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). To obtain a better understanding of proliferation and apoptosis of GECs, we examined immunohistochemical and in situ hybridization findings in puromycin aminonucleoside nephrosis (PAN) of rats. The minimal-change nephrotic syndrome model (PAN-MCNS) was induced by administering 5 subcutaneous injections of puromycin aminonucleoside (PA; each 1.5 mg/100 g B/W to one group of rats), whereas the FSGS model (PAN-FSGS) was induced by administering an additional 5 injections of PA to another group of rats. The cell kinetics of the GECs were assessed with labeling 5-bromo 2'-deoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). To investigate regulation of apoptosis in rats with PAN, we evaluated the expression of p53, Fas antigen, Fas ligand and Bc1-2. Rats with PAN-MCNS exhibited a significantly greater number of BrdU- and PCNA-labeled GECs as compared with control rats. In rats with PAN-FSGS, the number of PCNA-labeled GECs was greater than in rats with PAN-MCNS, but the number of BrdU-labeled GECs was lower. Apoptotic cells were occasionally observed in the sclerotic lesions, with the number being significantly higher in rats with PAN-FSGS than in rats with PAN-MCNS and control. Apoptotic cells were observed in the GECs of PAN-FSGS rats. However, they were negative for p53, Fas antigen, and Fas ligand. Immunohistochemical and in situ hybridization studies revealed a greater intraglomerular overexpression of Bc1-2 protein and bc1-2 mRNA in the PAN-FSGS rats as compared with control rats. These results suggest that insufficient proliferation and apoptosis in GECs may be involved in the progression of FSGS.