Molecular Mechanisms Related to Parturition-Induced Stress Urinary Incontinence

被引：37

作者：

Lin, Guiting ^{[1
]}

Shindel, Alan W. ^{[1
]}

Banie, Lia ^{[1
]}

Deng, Donna ^{[1
]}

Wang, Guifang ^{[1
]}

Hayashi, Narihiko ^{[1
]}

Lin, Ching-Shwun ^{[1
]}

Lue, Tom F. ^{[1
]}

机构：

[1] Univ Calif San Francisco, Dept Urol, Sch Med, Knuppe Mol Urol Lab, San Francisco, CA 94143 USA

来源：

EUROPEAN UROLOGY | 2009年 / 55卷 / 05期

关键词：

Birth trauma; Stress urinary incontinence; Molecular mechanisms oligo; microarray; Sprague-Dawley rat; Gene expression; VAGINAL DISTENSION; WOMEN; PREVALENCE; RAT;

D O I：

10.1016/j.eururo.2008.02.027

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 Design, setting, and participants: 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. Intervention: 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 (1) according to the results of cystometry. Measurements: 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). Results and limitations: 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. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：1213 / 1222

页数：10

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