Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction

Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction
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DOI:
10.1016/j.urology.2004.06.064
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发表时间:
2004-12-01
期刊:
影响因子:
2.1
通讯作者:
Takeda, M
Takeda, M
中科院分区:
医学4区
文献类型:
--
作者:
Araki, I;Du, SQ;Takeda, M

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目标。检查上皮钠通道 (ENaC) 是否在人膀胱中表达,以及其表达如何随出口梗阻而变化。逼尿肌不稳定的发生与膀胱出口梗阻有关。传入活动的增加是这种逼尿肌不稳定的可能机制之一。哺乳动物中表达的 ENaC 与多种机械感觉功能有关。方法。膀胱粘膜样本取自 9 名对照者和 9 名膀胱出口梗阻患者,并通过国际前列腺症状评分、前列腺体积和尿动力学测试进行验证。 7 名出口梗阻患者出现逼尿肌不自主收缩。使用免疫荧光染色检查 ENaC 蛋白的表达和定位。通过实时逆转录酶-聚合酶链反应评估 ENaC 基因表达的定量。结果。 α-ENaC、β-ENaC 和 γ-ENaC 蛋白在具有出口梗阻的人膀胱上皮中表达,而 α-ENaC 和 γ-ENaC 蛋白在对照膀胱中几乎未染色。分别在 9 个对照膀胱中的 1 个、6 个和 4 个中检测到 α-ENaC、β-ENaC 和 γ-ENaC mRNA。每个 ENaC mRNA 都清楚地存在于所有梗阻膀胱中。梗阻膀胱中各亚基的表达水平显着高于对照组。量化的 ENaC 表达与储存症状评分显着相关。结论。膀胱上皮中表达的 ENaC 可能与膀胱传入通路中的机械感觉转导有关,从而通过出口阻塞诱导逼尿肌不稳定。 (C) 2004 年爱思唯尔公司。
Objectives. To examine whether the epithelial sodium channel (ENaC) is expressed in the human urinary bladder and how its expression changes in association with outlet obstruction. Detrusor instability occurs in association with bladder outlet obstruction. The increase of afferent activity is one of the possible mechanisms for this detrusor instability. The ENaC expressed in mammals has been implicated in various mechanosensory functions.Methods. Specimens of urinary bladder mucosa were obtained from 9 controls and 9 patients with bladder outlet obstruction verified by the International Prostate Symptom Score, prostate volume, and urodynamic tests. In 7 patients with outlet obstruction, involuntary detrusor contraction was demonstrated. The expression and localization of ENaC proteins was examined using immunofluorescent staining. The quantification of ENaC gene expression was assessed by real-time reverse transcriptase-polymerase chain reaction.Results. The alpha-ENaC, beta-ENaC, and gamma-ENaC proteins were expressed in human urinary bladder epithelium with outlet obstruction, and the alpha-ENaC and gamma-ENaC proteins were virtually unstained in the control bladders. Alpha-ENaC, beta-ENaC, and gamma-ENaC mRNA were detected in 1, 6, and 4 of 9 control bladders, respectively. Each ENaC mRNA was clearly present in all obstructed bladders. The expression levels of each subunit in the obstructed bladders were significantly greater than those in controls. The quantified ENaC expression correlated significantly with the storage symptom score.Conclusions. The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction. (C) 2004 Elsevier Inc.