Apoptosis of Proliferative Cortical Tubular Epithelia in Chronic Progressive Nephrosis of Rats

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To investigate the role of apoptosis in the pathogenesis of rat chronic progressive nephrosis (CPN), the kidney of male F344/DuCrj rats, 19, 59, and 111 weeks of age, was examined histologically. In situ analysis for DNA fragmentation and proliferating cell nuclear antigen (PCNA) was performed simultaneously by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunohistochemistry, respectively. CPN was seen in all the kidneys of 59-week-old (n=6) and 111-week-old rats (n=16), correlating significantly (p<0.01) with age. There were apoptotic bodies (ABs) in the single-layered epithelia of dilated tubules (SLD) and the multi-layered epithelia (ML) of the cortical tubules. There were no ABs in any of the kidneys of the 19-week-old (n=5) or 59-week-old rats (n=6). Proliferative activity might have been enhanced in the single-layered and flattened epithelia, SLD, and ML of the cortical tubules in the kidneys of the 59-week-old rats (n=6) compared with that in 111-week-old rats (n=8). The correlations between the TUNEL-positive ratio and number of PCNA-positive cells, and age and the CPN grade were significant (p<0.01) exclusively in the ML. Thus, the results suggest that apoptosis occurs in the proliferative ML of rat CPN, and the pathological significance might be the removal of abnormal or excess cells.