In vivo hepatocyte growth factor gene transfer to bladder smooth muscle after bladder outlet obstruction in the rat: a morphometric analysis

J Urol. 2006 Sep;176(3):1230-5. doi: 10.1016/j.juro.2006.04.036.

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusions: These findings may imply a possible novel therapeutic strategy against bladder dysfunction arising in patients with bladder outlet obstruction.

MeSH terms

  • Animals
  • Collagen / metabolism
  • Gene Transfer Techniques
  • Hepatocyte Growth Factor / genetics*
  • Male
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Transforming Growth Factor beta / biosynthesis
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder Neck Obstruction / metabolism
  • Urinary Bladder Neck Obstruction / pathology
  • Urinary Bladder Neck Obstruction / therapy*

Substances

  • Transforming Growth Factor beta
  • Hepatocyte Growth Factor
  • Collagen