title: Molecular mechanisms related to parturition-induced stress urinary incontinence.
abstract: BACKGROUND
  The molecular mechanisms underlying stress urinary incontinence (SUI) at the tissue level are poorly understood.
  
  
  OBJECTIVE
  To study genetic and molecular alterations in the urethras of animals with experimentally induced SUI.
  
  
  METHODS
  Cohort analysis of primiparous 2-month-old female Sprague-Dawley rats with experimentally induced SUI versus those who did not develop SUI in a university research laboratory setting.
  
  
  METHODS
  Rats underwent intravaginal balloon dilation within 24 hours of parturition followed by bilateral ovariectomy one week later. Transvesical cystometry was performed 12 weeks after parturition. Rats were classified as continent (C) or incontinent (I) according to the results of cystometry.
  
  
  METHODS
  The expression of over 22,000 genes in urethral tissue from the two groups was assessed with the use of an oligo microarray. The expression of relevant genes was confirmed by real-time polymerase chain reaction. Protein expression of small mothers against decapentaplegic 2 (Smad2), one of the differentially expressed genes, was extensively studied by immunohistochemistry and Western blot analysis. Regulation of Smad2 activity by transforming growth factor-beta (TGF-beta) was assessed in cultured urethral smooth muscle cells (USMCs).
  
  
  CONCLUSIONS
  After intervention, 14 (58.3%) rats remained continent and 10 (41.7%) became incontinent. There were significant differences in the expression of 42 urethral genes between continent and incontinent rats. The expression of genes involved in the TGF cellular signaling pathway (Smad2), collagen breakdown (matrix metalloproteinase 13 [Mmp13]), and smooth muscle inhibition (regulator of G-protein signaling 2 [Rgs2]) was significantly increased in the incontinent group. SMAD2 protein expression was significantly upregulated in the incontinent rats. In cultured USMCs, SMAD2 phosphorylation and nuclear translocation increased after Tgf-beta treatment.
  
  
  CONCLUSIONS
  Genes important in inflammation, collagen breakdown, and smooth muscle inhibition are upregulated in the urethras of female rats with parturition-associated incontinence.
authors: Department of Urology, School of Medicine, University of California, San Francisco, CA 94143, USA. glin@urology.ucsf.edu
authors: Guiting
authors: G
authors: Lin
authors: Alan W
authors: AW
authors: Shindel
authors: Lia
authors: L
authors: Banie
authors: Donna
authors: D
authors: Deng
authors: Guifang
authors: G
authors: Wang
authors: Narihiko
authors: N
authors: Hayashi
authors: Ching-Shwun
authors: CS
authors: Lin
authors: Tom F
authors: TF
authors: Lue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008967:Molecular Biology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D036801:Parturition; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D040081:Protein Array Analysis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014550:Urinary Incontinence, Stress / Q000235:genetics* / Q000503:physiopathology
chemical_list: C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta