Do extracellular matrix protein expressions change with cyclic reproductive hormones in pelvic connective tissue from women with stress urinary incontinence?

Hum Reprod. 2006 May;21(5):1266-73. doi: 10.1093/humrep/dei485. Epub 2006 Feb 1.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Case-Control Studies
  • Connective Tissue / drug effects
  • Connective Tissue / metabolism*
  • Connective Tissue / pathology
  • Elastin / analysis
  • Elastin / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Fibroblasts / chemistry
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gonadal Hormones / pharmacology
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Latent TGF-beta Binding Proteins
  • Microfibrils / chemistry
  • Microfibrils / metabolism
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Pelvis*
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1
  • Urinary Incontinence, Stress / genetics
  • Urinary Incontinence, Stress / metabolism*
  • Urinary Incontinence, Stress / pathology
  • Vagina / chemistry
  • Vagina / drug effects
  • Vagina / metabolism

Substances

  • Extracellular Matrix Proteins
  • FBN1 protein, human
  • FBN2 protein, human
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Gonadal Hormones
  • Intracellular Signaling Peptides and Proteins
  • LTBP1 protein, human
  • LTBP2 protein, human
  • Latent TGF-beta Binding Proteins
  • Microfilament Proteins
  • RNA, Messenger
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Elastin