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 the smooth muscle layer of completely obstructed ureters, and to determine whether myocytes proliferate (hyperplasia) in the ureters 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 ureters. After ureteric ligation, five rats each were killed and examined at 0.5, 1, 2, 4, 8, 16 and 24 h after ligation. The proximal portion of the ureters was prepared for light and electron microscopy. The expression of c-Fos, c-Jun, c-Myc and Ki-67 antigen was assessed immunohistochemically. RESULTS: c-Fos and c-Jun were detected 2 h after ligation and the expression of these two proteins reached a maximum after 4 h, becoming undetectable 16 h after ligation. The expressions 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 24 h after ureteric ligation. The amount of rough endoplasmic reticulum (rER) in the ligated ureters increased soon after complete ligation and the increase continued throughout the period of ureteric obstruction (r = 0.9699, P < 0.001). The change in rER was also significantly correlated with the expression of c-Fos and c-Jun within 8 h after ligation. CONCLUSION: The expression of c-Fos and c-Jun, but not c-Myc, might contribute to the hypertrophy of the ureteric smooth muscle layer during the course of complete ureteric obstruction. There is no hyperplasia in ureteric smooth muscle in the early stages of obstructive uropathy.