Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women
Microarray analysis of differentially expressed genes in vaginal tissues from women with stress urinary incontinence compared with asymptomatic women
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DOI：
10.1093/humrep/dei276
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Polan, ML
中科院分区：
文献类型：
--
作者：
Chen, B;Wen, Y;Polan, ML
背景：女性盆底功能障碍导致压力性尿失禁(SUI)的病理生理机制是复杂的。有证据表明，SUI也有遗传易感性。我们试图从月经分泌期SUI妇女和无症状妇女的阴道组织中识别参与细胞外基质(ECM)代谢的差异表达基因。方法：采用基因芯片人类基因组U133寡核苷酸芯片，对5对绝经前、年龄匹配的SUI和可控性女性的阴道壁组织标本进行微阵列分析。结果：广泛的统计分析产生了79个差异表达基因的列表。Elafin、角蛋白16、XVI型胶原蛋白和PLAKAPIL1被一致鉴定为上调的ECM基因。Elafin是一种参与弹性蛋白降解途径和伤口愈合的丝氨酸蛋白酶抑制剂，在盆腔成纤维细胞中表达，并经Western印迹、定量竞争PCR和免疫荧光细胞染色证实。结论：参与弹性蛋白代谢的基因在SUI患者的阴道组织中差异表达，提示弹性蛋白重塑可能在SUI的分子病因学中起重要作用。
BACKGROUND: The pathophysiology of pelvic floor dysfunction resulting in stress urinary incontinence (SUI) in women is complex. Evidence suggests that there is also a genetic predisposition towards SUI. We sought to identify differentially expressed genes involved in extracellular matrix (ECM) metabolism in vaginal tissues from women with SUI in the secretory phase of menses compared with asymptomatic women. METHODS: Tissue samples were taken from the periurethral vaginal wall of five pairs of premenopausal, age-matched SUI and continent women and subjected to microarray analysis using the GeneChip Human Genome U133 oligonucleotide chip set. RESULTS: Extensive statistical analyses generated a list of 79 differentially expressed genes. Elafin, keratin 16, collagen type XVII and plakophilin 1 were consistently identified as up-regulated ECM genes. Elafin, a serine protease inhibitor involved in the elastin degradation pathway and wound healing, was expressed in pelvic fibroblasts and confirmed by Western blot, quantitative competitive PCR and immunofluorescence cell staining. CONCLUSIONS: Genes involved in elastin metabolism were differentially expressed in vaginal tissue from women with SUI, suggesting that elastin remodelling may be important in the molecular aetiology of SUI.