Decreased gene expression of fibrillin-1 in stress urinary incontinence.
OBJECTIVE
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.
Söderberg
Marie Westergren
MW
Department of Woman and Child Health, Karolinska Institutet Karolinska University Hospital Solna, Stockholm, Sweden. marie.westergren-soderberg@sodersjukhuset.se
Byström
Birgitta
B
Hammarström
Margareta
M
Malmström
Anders
A
Ekman-Ordeberg
Gunvor
G
D000328:Adult; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005786:Gene Expression Regulation; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D014550:Urinary Incontinence, Stress / Q000235:genetics*; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines