transforming-growth-factor-beta and Urinary-Incontinence

Prior studies demonstrate increased incidence of urinary incontinence (UI) in the geriatric population which affects their quality of life. Pathophysiology of UI in the geriatric population and the underlying molecular mechanisms are still unclear. To elucidate these mechanisms, we performed a pre-clinical study in a rabbit model and the objectives were to (i) determine the effect of aging as well as multiparity on urethral sphincter muscle thickness and urethral closing pressure (UCP); (ii) examine the role of fibrosis and atrophy; and (iii) elucidate the molecular pathways that mediate fibrosis and atrophy in the urethral tissue.. New Zealand White female rabbits (n = 6 each; young 6-12 months and old over 30 months of age) were anesthetized and urethral muscle thickness and sphincter closure function were measured. Rabbits were then sacrificed and urethral tissues (bladder neck and mid-urethra) were collected to process for immunostaining as well as for molecular studies for markers for fibrosis (β-catenin which is an important mediator of Wnt signaling, Collagen-1, and TGF-β) and atrophy (MuRF-1).. Our studies showed a significant decrease in the urethral sphincter muscle thickness and closure function with age. Age-related increase in protein and mRNA expression levels of fibrosis, as well as atrophy markers were observed in the bladder neck and mid-urethral tissues.. Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals.

Topics: Age Factors; Animals; Female; Parity; Pregnancy; Quality of Life; Rabbits; Transforming Growth Factor beta; Urethra; Urinary Bladder; Urinary Incontinence; Wnt Signaling Pathway

Alterations in collagen synthesis and metabolism have previously been reported in patients with pelvic organ prolapse (POP) and/or urodynamic stress incontinence (USI). Since urinary incontinence does not always associate with POP, the objective of this study was to examine connective tissues from patients with USI plus POP, and patients with prolapse only.. Biopsies from the uterosacral ligaments were obtained during the operation from POP patients (n =28), and from continent women (control group, n =12) who underwent surgery for other benign reasons. POP patients were classified following urodynamic tests and symptom questionnaire with respect to the presence (n =14) or absence (n =14) of USI. N-terminal propeptides of collagen (PINP and PIIINP), TGF-beta and leptin were measured in plasma. Hydroxyproline and glycosaminoglycan (GAGs) concentrations and total hexosaminidase activity were measured in tissue samples. Histological sections were prepared using Masson's trichrome technique, and digitised solutions were used for imaging provided by Soft Imaging System GmBh. Statistical evaluations were made by the Kruskal-Wallis test.. A significant decrease in hydroxyproline content was found in USI+POP women in comparison to controls (p<0.05). In contrast, histopathological examination revealed an increased density of collagen in USI+POP patients. Hexosaminidase activity was decreased in both groups with POP, but no change in the amount of GAGs was observed. Markers of collagen synthesis (PINP, PIIINP), and factors related to the collagen synthesis (TGF-beta, leptin) remained unaltered.. Our biochemical and morphological findings suggest a different organisation of collagen fibres in tissues of patients with USI+POP, when compared with both the controls and the POP patients.

Topics: Biopsy; Collagen; Connective Tissue; Female; Glycosaminoglycans; Hexosaminidases; Humans; Hydroxyproline; Leptin; Middle Aged; Statistics, Nonparametric; Transforming Growth Factor beta; Urinary Incontinence; Uterine Prolapse