Decreased gene expression of fibrillin-1 in stress urinary incontinence.

ABSTRACT

AIMS: Studies to show impairments in the pelvic floor extracellular matrix (ECM) associated with stress urinary incontinence (SUI) has earlier been performed, but the results are contradictory. Collagen I and III, the elastin associated proteins fibrillin-1 and fibulin-5 and the small leucine-rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin are involved in giving the tissue its mechanical properties. Their gene signals and tissue localizations were investigated. METHODS: Para-urethral punch biopsies were obtained from 24 women, 12 pre- and 12 postmenopausals, during surgery for SUI. As controls, biopsies were collected from 14 women, 8 pre- and 6 postmenopausals, undergoing surgery for other benign conditions. The mRNA expression by real-time RT-PCR and protein localization by immunohistochemistry were analyzed concerning collagen I and III, the small leucine rich repeat proteoglycans (SLRPs) decorin, lumican and fibromodulin and the elastic fiber associated proteins fibulin-5 and fibrillin-1. Statistical comparisons controlled for age changes in gene expressions. RESULTS: A significant decrease in mRNA expression of fibrillin-1 was discovered in all SUI women compared to all controls, P = 0.03. All molecules were down-regulated by age, but no other differences between SUI and controls reached significance. All proteins were adequately expressed by immunohistochemistry. A weaker staining for fibrillin-1 was seen in the pre-menopausal SUI group compared to the pre-menopausal controls. CONCLUSIONS: A decreased gene signal and weaker immunoreactivity for fibrillin-1, important for the elastic fiber assembly, was discovered in women with SUI. Loss of tissue elasticity could lead to increased urethra hypermobility and SUI.