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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Case-Control Studies
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Collagen Type I / antagonists & inhibitors*
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Collagen Type I / biosynthesis
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Collagen Type I / genetics
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Collagen Type III / antagonists & inhibitors*
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Collagen Type III / biosynthesis
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Collagen Type III / genetics
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Extracellular Matrix / drug effects
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Extracellular Matrix / metabolism
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Extracellular Matrix / pathology
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Female
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Fibroblasts / pathology
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Flavonoids / pharmacology
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Gene Expression Regulation
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Humans
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MAP Kinase Signaling System*
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Middle Aged
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / genetics
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / genetics
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Mitogen-Activated Protein Kinase 3 / metabolism*
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Phosphorylation
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Primary Cell Culture
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Protein Kinase Inhibitors
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Urinary Incontinence, Stress / genetics
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Urinary Incontinence, Stress / metabolism*
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Urinary Incontinence, Stress / pathology
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Vagina / drug effects
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Vagina / metabolism
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Vagina / pathology
Substances
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Collagen Type I
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Collagen Type III
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Flavonoids
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Protein Kinase Inhibitors
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RNA, Messenger
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one