The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence

J Int Med Res. 2013 Aug;41(4):1242-51. doi: 10.1177/0300060513493995. Epub 2013 Jul 18.

Abstract

Objective: To investigate the role of extracellular-regulated protein kinase (ERK)1/2 and phosphorylated (p)-ERK1/2 in the pathogenesis of female stress urinary incontinence (SUI).

Methods: Anterior vaginal wall tissue was collected from women with SUI and control subjects. Immunohistochemistry and Western blotting were performed for p-ERK1/2. Primary vaginal fibroblast cultures were incubated in the presence or absence of PD98059 (an inhibitor of ERK kinase) and levels of collagen I and III mRNA and protein were examined by quantitative reverse transcription-polymerase chain reaction and Western blot, respectively.

Results: Levels of p-ERK1/2 were significantly lower in vaginal wall tissue from patients with SUI (n = 10) compared with controls (n = 10). PD98059 treatment significantly reduced levels of collagen I and III mRNA and protein.

Conclusions: Female SUI is associated with reduced levels of p-ERK1/2 compared with controls, and inhibition of the ERK1/2 signalling pathway inhibits collagen type I and III synthesis in vaginal wall fibroblasts.

Keywords: ERK1/2; Stress urinary incontinence; anterior vaginal wall; collagen; extracellular-regulated protein kinase 1/2; fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Collagen Type I / antagonists & inhibitors*
  • Collagen Type I / biosynthesis
  • Collagen Type I / genetics
  • Collagen Type III / antagonists & inhibitors*
  • Collagen Type III / biosynthesis
  • Collagen Type III / genetics
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Flavonoids / pharmacology
  • Gene Expression Regulation
  • Humans
  • MAP Kinase Signaling System*
  • Middle Aged
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phosphorylation
  • Primary Cell Culture
  • Protein Kinase Inhibitors
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Urinary Incontinence, Stress / genetics
  • Urinary Incontinence, Stress / metabolism*
  • Urinary Incontinence, Stress / pathology
  • Vagina / drug effects
  • Vagina / metabolism
  • Vagina / pathology

Substances

  • Collagen Type I
  • Collagen Type III
  • Flavonoids
  • Protein Kinase Inhibitors
  • RNA, Messenger
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one