Sodium restriction decreases AP-1 activation after nephron reduction in the rat: Role in the progression of renal lesions

Renal hyperplasia and hypertrophy are early events after nephron reduction which precede progressive destruction of the remnant kidney. Restriction of dietary sodium content was shown to reduce renal lesions following nephron reduction. AP-1 is a transcription factor, resulting from heterodimerizati on of fos and jun proteins, which mediates the effects of mitogenic growth factors. To elucidate the role of AP-1 in growth processes involved in rena l deterioration, we evaluated whether restriction of dietary sodium content (0.25 vs. 0.50% sodium w/w) affected AP-1-DNA binding and hyperplasia in t he remnant kidney after nephron reduction (70% nephrectomy). Cell prolifera tion, evaluated by PCNA immunostaining, increased progressively from day 7 to day 60 in glomeruli, proximal and distal tubules and loops of Henle of n ephrectomized (Nx) rats compared to control sham-operated (C) animals. AP-1 -DNA binding activity increased 7 and 14 days after surgery, but it was red uced below C values at day 60. c-fos and c-jun expression were also reduced in Nx rats at day 60. Sodium restriction significantly reduced the number of PCNA-stained cells in glomeruli and tubules at days 14 and 60, but not a t day 7, whereas it decreased AP-1 activation at all times of the study. Th is effect was associated to a marked reduction of renal lesions in Nx rats. In conclusion, we showed that, after nephron reduction, the beneficial eff ect of sodium restriction was associated with a reduction of hyperplasia an d AP-1 activation, but that the latter did not parallel delayed cell prolif eration rate in remaining nephrons. Thus, we propose that different transdu ction pathways are involved in cell proliferation after nephron reduction, according to the time of evolution of renal lesions. Copyright (C) 2000 S. Karger AG, Basel.