Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence?
BACKGROUND
To evaluate differential expression of transforming growth factor (TGF-beta1), latent transforming factor-binding proteins (LTBP-1, LTBP-2) and elastin microfibril components (fibrillin-1 and fibrillin-2) in vaginal tissue from women with stress urinary incontinence (SUI).


METHODS
In this case-control study, vaginal tissue from women in both phases of the menstrual cycle was obtained. Messenger RNA (mRNA) expressions of LTBP-1, LTBP-2, fibrillin-1, fibrillin-2 and TGF-beta1 were determined by relative real-time quantification PCR. Tissue localization was analysed by immunohistochemistry, and semiquantitative protein expression was evaluated by Western blot analysis.


RESULTS
Vaginal wall fibroblasts synthesized all proteins tested. LTBP-1, LTBP-2 and TGF-beta1 co-localized with elastin microfibrils, fibrillin-1 and fibrillin-2 in the extracellular matrix. LTBP-1 mRNA and protein expressions were higher in control versus women affected with SUI in the proliferative phase (P = 0.04), while in the secretory phase, mRNA expression in cases was higher (P = 0.04). Fibrillin-1 mRNA was higher in women affected by SUI versus controls in both phases, but no statistical differences in fibrillin-1 protein expression were observed between the two groups in either phase. LTBP-2 and TGF-beta1 mRNA expressions showed the same trends as LTBP-1.


CONCLUSIONS
LTBP-1, LTBP-2, TGF-beta1, fibrillin-1, and fibrillin-2 expressions are hormonally regulated in vaginal wall fibroblasts and differ in women affected by SUI when compared to controls. These data suggest a mechanism to regulate TGF-beta1 activity in pelvic connective tissue.
Wen
Yan
Y
Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305-5317, USA. yanwen@stanford.edu
Polan
Mary Lake
ML
Chen
Bertha
B
D016022:Case-Control Studies; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004549:Elastin / Q000032:analysis / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005347:Fibroblasts / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D042341:Gonadal Hormones / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D053779:Latent TGF-beta Binding Proteins; D020894:Microfibrils / Q000737:chemistry / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010388:Pelvis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014550:Urinary Incontinence, Stress / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014621:Vagina / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D054392:Adipokines
D004549:Elastin; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D042341:Gonadal Hormones; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C509032:LTBP1 protein, human; C509035:LTBP2 protein, human; C508960:TGFB1 protein, human