In Vivo Hepatocyte Growth Factor Gene Transfer to Bladder Smooth Muscle After Bladder Outlet Obstruction in the Rat: A Morphometric Analysis

Abstract

We determined whether hepatocyte growth factor gene transfer after partial bladder outlet obstruction would prove effective for decreasing transforming growth factor-beta expression and consequently decreasing collagen deposition in partially obstructed rat bladders. Ten-week-old male Sprague-Dawley rats were divided into 3 groups of 10 each, including group 1--sham operation, group 2--bladder outlet obstruction for 4 weeks and group 3--hepatocyte growth factor gene transfer after bladder outlet obstruction. Two weeks after the onset of bladder outlet obstruction in group 3 hepatocyte growth factor-liposome complex (50 microg human hepatocyte growth factor cDNA) was injected into the smooth muscle of the rats. We noted no difference between groups 2 and 3 with regard to the ratio of bladder weight to body weight. The ratio in groups 2 and 3 was significantly higher than in group 1 (p = 0.043). The mean percent of collagen area +/- SE was 36.32% +/- 1.83%, 27.90% +/- 2.66% and 8.97% +/- 3.35% in groups 1 to 3, respectively (p <0.05). Relative hepatocyte growth factor and c-met mRNA and protein expression were higher in group 3 than in groups 1 and 2. However, the expression of transforming growth factor-beta1 mRNA and protein was higher in group 2 than in groups 1 and 3. These findings may imply a possible novel therapeutic strategy against bladder dysfunction arising in patients with bladder outlet obstruction.