Extracellular matrix changes in urethral stricture disease.

PURPOSE Glycosaminoglycans (GAGs) and collagen are major components of the extracellular matrix and they have key roles in fibrotic diseases. Little is known about the molecular environment in urethral stricture and the majority of the studies available focused on collagen analysis. However, to our knowledge there are no data on GAG composition in urethral stricture disease. MATERIALS AND METHODS Bulbar urethral strictured segments were obtained from 10 patients 18 to 61 years old (mean age 41.8) who underwent end-to-end anastomotic urethroplasty. GAGs in dry tissue samples were extracted by papain digestion and cetylpyridinium chloride/ethanol precipitation. The concentration of total GAGs was assessed by hexuronic acid assay and expressed in microg. hexuronic acid per mg. dry tissue, while the proportion of sulfated GAGs was determined by agarose gel electrophoresis. The concentration of hyaluronic acid was determined by ion exchange chromatography and total tissue collagen was estimated as its hydroxyproline content. The control group consisted of 10 bulbar urethras obtained from fresh normal cadavers 22 to 53 years old (mean age 32.8). RESULTS Mean total GAG concentration plus or minus standard deviation in the stricture group was 1.09 +/- 0.13, which was significantly lower than in controls (p <0.05). While the predominant GAG in normal bulbar urethras was hyaluronic acid, dermatan sulfate predominated in strictured urethras (mean 44.1% +/- 8.4 and 45.6% +/- 7.7%, respectively). Hyaluronic acid decreased 49.9% and dermatan sulfate increased 68.3%. There were no significant changes in the concentration of heparan sulfate or chondroitin sulfate in normal and strictured bulbar urethras. Mean total collagen significantly increased 32.3% (p <0.05). CONCLUSIONS Composition changes in GAGs in strictured urethras could contribute to the noncompliant nature of urethral scar tissue and cause functional changes. These results may be useful for defining new targets for therapy for urethral stricture disease.