EARLY GENETIC AND CELLULAR-RESPONSES IN THE SMOOTH-MUSCLE LAYER OF OBSTRUCTED URETERS IN A RAT MODEL OF OBSTRUCTIVE UROPATHY

Objective To investigate the early genetic and cellular responses in t he smooth muscle layer of completely obstructed meters, and to determi ne whether myocytes proliferate (hyperplasia) in the meters during the early stage of obstructive uropathy. Materials and methods The study comprised 35 female Sprague-Dawley rats which had undergone unilateral ligation of their meters. After ureteric ligation, five rats each wer e killed and examined at 0.5, 1, 2, 4, 8, 16 and 24 h after ligation. The proximal portion of the meters was prepared for light and electron microscopy. The expression of c-Fos, c-jun, c-Myc and Ki-67 antigen w as assessed immunohistochemically. Results c-Fos and c-Jun were detect ed 2 h after ligation and the expression of these two proteins reached a maximum after 4 h, becoming undetectable 16 h after ligation. The e xpressions of c-Fos and c-Jun were strongly correlated (r=0.9854, P<0. 001). The expressions were of c-Myc and Ki-67 antigen was not detected within 24h after ureteric ligation. The amount of rough endoplasmic r eticulum (rER) in the ligated ureters increased soon after complete li gation and the increase continued throughout the period of ureteric ob struction (r=0.9699, P<0.001). The change in rER was also significantl y correlated with the expression of c-Fos and c-Jun within 8 h after l igation. Conclusion The expression of c-Fos and c-Jun, but not c-Myc, might contribute to the hypertrophy of the ureteric smooth muscle laye r during the course of complete ureteric obstruction. There is no hype rplasia in ureteric smooth muscle in the early stages of obstructive u ropathy.