title: Role of proteoglycans in the organization of periurethral connective tissue in women with stress urinary incontinence.
abstract: OBJECTIVE
  Connective tissue consists of fibroblasts and extracellular matrix (ECM) with collagen and elastic fibers, glycoproteins and proteoglycans (PGs) and it is considered an important factor of the supportive structures of the genitourinary region. Since PGs are essential for the organization of the collagen fibrils in the ECM, we investigated the presence of two PGs, fibromodulin and lumican, and of collagen type I in the periurethral connective tissue from women with stress urinary incontinence (SUI), compared to asymptomatic controls.
  
  
  METHODS
  Thirty-two patients participated in the study and they were divided into four groups: premenopausal incontinents, premenopausal controls, postmenopausal incontinents and postmenopausal controls. All patients underwent gynaecologic surgical procedures and punch biopsies from the periurethral tissue were obtained. Immunohistochemistry for collagen type I, fibromodulin and lumican was performed on the histological slides.
  
  
  RESULTS
  In premenopausal incontinents the immunoreactivity for collagen type I was weaker with an irregular distribution compared to premenopausal controls; while for fibromodulin, the staining was stronger in premenopausal incontinents than in premenopausal controls. Between the two postmenopausal groups there was not a significant difference in the intensity of collagen type I and fibromodulin staining that instead were less strong than in premenopausal groups. Lumican staining had the same distribution in the four groups.
  
  
  CONCLUSIONS
  Our results suggest an altered remodelling of connective tissue in the periurethral region of premenopausal patients with SUI, with a significant decrease of collagen content and an irregular organization and distribution of the collagen fibrils, compared to premenopausal controls. In the SUI patients this abnormal ECM remodelling, mainly related to the observed change in PGs expression, might affect significantly the tensile strength of the connective tissue and consequently the support that is provided by the urogenital suspensory apparatus to urethra and bladder base. Moreover, the significant decrease in collagen type I content in postmenopausal patients respect to premenopausal patients, suggests that age and hormonal factors could contribute to the pathological modifications of the supportive genitourinary connective tissues in the SUI patients.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Science, II University of Naples, Naples, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trabucco
authors.forename: Marie
authors.initials: M
authors.lastname: Soderberg
authors.forename: Luigi
authors.initials: L
authors.lastname: Cobellis
authors.forename: Marco
authors.initials: M
authors.lastname: Torella
authors.forename: Birgitta
authors.initials: B
authors.lastname: Bystrom
authors.forename: Gunvor
authors.initials: G
authors.lastname: Ekman-Ordeberg
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.forename: Nicola
authors.initials: N
authors.lastname: Colacurci
mesh_terms: D000328:Adult; D000368:Aged; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D002979:Climacteric / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D003238:Connective Tissue / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D000071235:Fibromodulin; D006801:Humans; D007124:Immunoenzyme Techniques; D007632:Keratan Sulfate / Q000378:metabolism; D000071234:Lumican; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism*; D014521:Urethra / Q000473:pathology*; D014550:Urinary Incontinence, Stress / Q000473:pathology*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; C000604330:FMOD protein, human; C000604306:LUM protein, human; D000071234:Lumican; D011509:Proteoglycans; D000071235:Fibromodulin; D007632:Keratan Sulfate