APOPTOSIS AND EXPRESSION OF BAX PROTEIN AND FAS ANTIGEN IN GLOMERULI OF A REMNANT-KIDNEY MODEL

The role of apoptosis in glomerular cell depletion associated with a d ecrease in renal function is still controversial. To examine the invol vement of apoptosis in renal disease, the occurrence of apoptosis duri ng the progression of renal insufficiency as well as the expression of Bar protein and Fas antigen that are related to the apoptosis were in vestigated using five-sixths nephrectomized rats, one of the progressi ve renal disease models. Serum creatinine was significantly elevated t o a level approximately five-fold higher than that in the sham-operate d group on day 1 after the five-sixths nephrectomy and then maintained at a level approximately mio-to threefold higher until day 56 and the n elevated further to a level eight-fold higher on day 96 after nephre ctomy as compared with the sham-operated group. The total number of gl omerular cells was significantly increased from day 7 to day 56 after nephrectomy and then returned to the level of the sham-operated group by day 96. The number of PCNA-positive cells (a marker of proliferatin g cells) in the glomeruli was significantly increased from day 7 to da y 28 after nephrectomy; the highest level was observed on day 7, and t he numbers then decreased gradually. Apoptotic cells, which were repre sented by TUNEL-positive cells, as well as apoptotic bodies were persi stently increased with time after nephrectomy in the glomeruli of neph rectomized rats; apoptotic cells could hardly be observed in the sham- operated group. Therefore, glomerular cell proliferation appeared to b egin immediately after nephrectomy and to continue until day 28 at a l evel high enough to overcome the decrease in the number of glomerular cells due to apoptosis, since the total number of glomerular cells was apparently high until day 56. On day 96, the decrease in the number o f glomerular cells probably becomes predominant over cell proliferatio n, since apoptosis continuously increased with time after nephrectomy. The events on day 96 may be associated with the severely decreased re nal function which was represented by the explosive increase in the se rum creatinine level on the same day. The number of Fas antigen positi ve glomerular cells was increased from day 1 after nephrectomy and rea ched a plateau on day 21. The number of Bar protein positive glomerula r cells was generally increased with time after nephrectomy, but the n umber was slightly decreased on day 21. The theory that the expression of Bar protein is correlated with apoptosis appears to fit the case o f progressive renal insufficiency.