Age and multiparity related urethral sphincter muscle dysfunction in a rabbit model: Potential roles of TGF-β and Wnt-β catenin signaling pathways
| Autor: | Johnny Fu, Valmik Bhargava, Yaozhi Wang, Michael E. Albo, My-Uyen Lilly Nguyen, Mahadevan Rajasekaran |
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| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
Urology Urinary Bladder 030232 urology & nephrology Urinary incontinence 03 medical and health sciences 0302 clinical medicine Atrophy Urethra Fibrosis Pregnancy Transforming Growth Factor beta Medicine Animals Wnt Signaling Pathway 030219 obstetrics & reproductive medicine business.industry Urethral sphincter Wnt signaling pathway Age Factors medicine.disease Pathophysiology Neck of urinary bladder Parity medicine.anatomical_structure Urinary Incontinence Quality of Life Sphincter Female Neurology (clinical) Rabbits medicine.symptom business |
| Zdroj: | Neurourology and urodynamics. 38(2) |
| ISSN: | 1520-6777 |
| Popis: | AIMS 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. METHODS 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). RESULTS 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. CONCLUSIONS Age and multiparity related increase in fibrosis and atrophy of urethral sphincter muscles may contribute to impaired urethral closure function seen in old animals. |
| Databáze: | OpenAIRE |
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