Transforming growth factor β1 and extracellular matrix protease expression in the uterosacral ligaments of patients with and without pelvic organ prolapse

Female Pelvic Med Reconstr Surg. 2015 Jan-Feb;21(1):53-8. doi: 10.1097/SPV.0000000000000130.

Abstract

Objectives: This study was undertaken to evaluate the expression of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls.

Methods: Under an institutional review board approval, USL samples were obtained from women undergoing vaginal hysterectomy for stage 2 or greater POP (cases, n = 21) and from women without POP undergoing vaginal hysterectomy for benign indications (controls, n = 19). Hematoxylin and eosin and trichrome staining were performed on the USL sections, and the distribution of smooth muscle and fibrous tissue were quantified. Immunohistochemical staining was performed using anti-TGF-β1 and anti-MMP-9 antibodies. The expressions of TGF-β1 and MMP-9 were evaluated by the pathologist, who was blinded to all clinical data.

Results: Transforming growth factor β1 expression positively correlated with MMP-9 expression (R = 0.4, P = 0.01). The expressions of TGF-β1 and MMP-9 were similar in subjects with POP versus controls. There was a significant increase in fibrous tissue (P = 0.008) and a corresponding decrease in smooth muscle (P = 0.03), associated with increasing age. The TGF-β1 expression, but not MMP-9 expression, also significantly increased with age (P = 0.02).

Discussion: Although our study uncovered age-related alterations in USL composition and TGF-β1 expression, there was no difference in the expression of TGF-β1 or MMP-9 in the subjects with POP versus controls.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Case-Control Studies
  • Extracellular Matrix / enzymology
  • Female
  • Fibrosis / metabolism
  • Humans
  • Ligaments / chemistry*
  • Ligaments / enzymology*
  • Ligaments / pathology
  • Matrix Metalloproteinase 9 / analysis*
  • Middle Aged
  • Muscle, Smooth / chemistry
  • Muscle, Smooth / enzymology
  • Pelvic Organ Prolapse / metabolism*
  • Prospective Studies
  • Single-Blind Method
  • Transforming Growth Factor beta1 / analysis*

Substances

  • Transforming Growth Factor beta1
  • Matrix Metalloproteinase 9