ALTERATION OF THE INSULIN-LIKE GROWTH FACTOR SYSTEM OF MITOGENS IN HYPERPLASTIC BLADDERS OF PARAPLEGIC RATS

Abstract

Smooth muscle cells of the bladder retain the ability to proliferate in response to injury or mechanical stimulation. Insulin-like growth factor (IGF) I is a mitogenic and hypertrophic agent for smooth muscle cells. The purpose of this study is to examine if spinal cord injury could lead to bladder hypertrophy via the IGF system. The study involved spinal cord transection of female Sprague Dawley rats (approximately 250 to 300 gm.). Six weeks following surgery the urinary bladder was collected. Northern and Western blotting, and IGF-I receptor (IGF-IR) affinity labeling were used to determine the expression of the IGF system, IGFBP levels, and IGF-IR levels respectively. Chronic spinal cord injury leads to an increase in the wet weight of the bladder and in the level of proliferation cell nuclear antigen expression. IGF-I mRNA levels increase, while IGFBP 3 and 5 mRNA and protein levels dramatically decrease. The gene expression of IGFBP 2 and 4 varies from rat to rat, and IGF-IR expression slightly increases. Our results suggest that following spinal cord injury, overexpression of IGF-I and underexpression of IGFBP 3 and 5 may lead to hyperplasia of the smooth muscle layer of the bladder.