title: Extracellular matrix expression of human prolapsed vaginal wall.
abstract: OBJECTIVE
  To compare the mRNA expression of extracellular matrix (ECM) proteins in postmenopausal prolapsed versus non-prolapsed anterior vaginal wall (AVW) tissue. We hypothesized that the weakening of the tissue leading to prolapse was due to decreased collagen production from a downregulation at the transcriptional level.
  
  
  METHODS
  Following IRB approval, full thickness samples of redundant AVW were excised from consecutive age-equivalent, postmenopausal, women undergoing cystocele repair (prolapse, stage III or IV), or radical cystectomy (control, no clinical findings of prolapse). Total RNA was isolated, cDNA was synthesized, and quantitative real-time polymerase chain reaction (PCR) was conducted to assess the mRNA expression of collagens type I and III, pro-elastin, MMP3, MMP10, and MMP11. The significance of the difference of mRNA expression between prolapse and control tissues was tested using Student's t-test followed by Mann-Whitney Rank Sum Test.
  
  
  RESULTS
  A 5.3-fold increase in collagen type I mRNA was found in prolapse (n = 47) over control (n = 7) tissues (P = 0.009). Type III collagen mRNA was also significantly increased to a 3.3 times higher level (P = 0.017). The ratio of type III to type I was decreased from 15.6 in controls to 9.7 in prolapse. An increasing trend in pro-elastin and MMP mRNA expression was found in prolapse, but this was not statistically significant.
  
  
  CONCLUSIONS
  In this controlled study, the increase found in collagen mRNA expression disproved our hypothesis. To the contrary, this defective prolapsed tissue can signal its need for ECM replenishment. The message, however, is not being effectively translated to assist in tissue remodeling.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical School, Dallas, Texas 75390-9110, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mosier
authors.forename: Victor K
authors.initials: VK
authors.lastname: Lin
authors.forename: Philippe
authors.initials: P
authors.lastname: Zimmern
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000235:genetics / Q000378:metabolism; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014596:Uterine Prolapse / Q000235:genetics / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D004549:Elastin; D053507:Matrix Metalloproteinase 11; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D053506:Matrix Metalloproteinase 10