UC San Diego
Role of Fibrosis and Atrophy in Injury & Diabetes Related Pelvic and Urogenital Disorders in Men
- Author(s): To, Sarah
- Advisor(s): Rajasekaran, Mahadevan
- et al.
Dysfunction of the pelvic floor muscles represents a significant risk factor for the development of incontinence (UI) and sexual dysfunction (SD) in geriatric populations. Specifically, diabetes and injury-related atrophy and fibrosis of the urogenital muscles have been implicated in the development of UI and SD. Although the loss of muscle mass is a clear indication of disorder, the precise cellular mechanisms that underlie manifestations of such the conditions remains elusive. Nevertheless, certain molecular pathways such as Wnt and TGF-β have already been found to contribute to the pathogenesis of fibrosis. The objective of this study was to ascertain the roles of key atrophic and fibrotic effectors in the expression of the involved pathways. Rabbit models were used to establish an injury model of urogenital muscle dysfunction and fibrotic mechanisms. Injured rabbits were sacrificed to harvest urogenital tissue samples. Human penile tissues were also collected from deidentified patients undergoing prosthesis. Protein expression was determined using immunostaining and western blot analysis for its quantification. Immunological studies demonstrated upregulation of fibrotic and atrophy pathways involving Wnt and TGF-β pathways, confirming increased fibrogenic pathology in these samples. Urogenital muscle atrophy/fibrosis can greatly impact continence as well as sexual functions. Understanding of such mechanisms may optimize development of potential interventions.