The Impact of Iatrogenic Urothelial Trauma on Urinary Levels of Transforming Growth Factor-Alpha

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Abstract
Growth factors are important regulators of epithelial cell biology. We postulated that iatrogenic bladder manipulations may alter urinary growth factor levels and thereby influence both normal and neoplastic urothelium. Using a rat model we studied the effects of various types of urothelial injury, corresponding to bladder catheterization, cystoscopy, fulguration, and chronic indwelling catheterization (Groups B, C, D, and E respectively) on levels of urinary transforming growth factor-alpha (uTGFa). Urine samples collected circa the time of transurethral bladder manipulation were analyzed for protein, creatinine (Cr), and TGFa. Results in experimental groups were compared to control values (group A). Peak concentrations of uTGFa uniformly occurred on the day of surgery and represented 176%, 196%, 726%, 461% and 916% increases relative to pre-operative values in groups A, B, C, D and E respectively. Total uTGFa (nM/mg. Cr) was maximal on experimental day 0 in groups A, B, C, D and day 2 in group E (102%, 114%, 227%, 290% and 976% change from baseline respectively). Compared to control, levels of uTFGFa were significantly elevated on day 0 in the fulguration group, and day 0 and 2 in the chronic catheterization animals (p less than .05). Nonsignificant elevations of uTGFa relative to control were based in all groups through day 7. The chronic catheterization levels remained significantly elevated, compared to control, over the duration of the study (ANOVA, p less than .05). Urinary protein levels correlated with the severity of the injury and showed a strong positive correlation with uTGFa (p = .0001). This study demonstrated a clear impact of iatrogenic urothelial trauma on urinary levels of TGFa.