Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women.
BACKGROUND
The pathophysiology of pelvic floor dysfunction resulting in stress urinary incontinence (SUI) in women is complex. Evidence suggests that there is also a genetic predisposition towards SUI. We sought to identify differentially expressed genes involved in extracellular matrix (ECM) metabolism in vaginal tissues from women with SUI in the secretory phase of menses compared with asymptomatic women.


METHODS
Tissue samples were taken from the periurethral vaginal wall of five pairs of premenopausal, age-matched SUI and continent women and subjected to microarray analysis using the GeneChip Human Genome U133 oligonucleotide chip set.


RESULTS
Extensive statistical analyses generated a list of 79 differentially expressed genes. Elafin, keratin 16, collagen type XVII and plakophilin 1 were consistently identified as up-regulated ECM genes. Elafin, a serine protease inhibitor involved in the elastin degradation pathway and wound healing, was expressed in pelvic fibroblasts and confirmed by Western blot, quantitative competitive PCR and immunofluorescence cell staining.


CONCLUSIONS
Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.
Chen
Bertha
B
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA. bchen@stanford.edu
Wen
Yan
Y
Zhang
Zhaomei
Z
Guo
Yaqian
Y
Warrington
Janet A
JA
Polan
Mary Lake
ML
D000328:Adult; D001324:Autoantigens / Q000032:analysis / Q000235:genetics; D005109:Extracellular Matrix / Q000737:chemistry / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D053536:Keratin-16; D007633:Keratins / Q000032:analysis / Q000235:genetics; D008875:Middle Aged; D024041:Non-Fibrillar Collagens / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D051191:Plakophilins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation; D014550:Urinary Incontinence, Stress / Q000235:genetics*; D014621:Vagina / Q000378:metabolism*; D000097805:Collagen Type XVII
D001324:Autoantigens; D053536:Keratin-16; D007633:Keratins; D024041:Non-Fibrillar Collagens; D051191:Plakophilins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; D000097805:Collagen Type XVII; C507431:KRT16 protein, human