Maake C, Landman M, Wang X, Schmid D M, Ziegler U, John H
Institute of Anatomy, University of Zürich, Zürich, Switzerland.
J Urol. 2006 Mar;175(3 Pt 1):1152-7. doi: 10.1016/S0022-5347(05)00315-0.
We established the expression pattern of smoothelin, a marker protein for contractile smooth muscle cells, in the human detrusor and investigated its possible impact on bladder overactivity.
Detrusor samples of 13 overactive bladders (sensory urge and detrusor instability) were obtained before botulinum toxin injection and compared to those of 8 normally contractile, nonobstructed bladders obtained during radical cystectomy. Smoothelin mRNA expression patterns were investigated by Northern blot and variant specific reverse transcriptase-polymerase chain reaction as well as by quantitative reverse transcriptase-polymerase chain reaction on laser capture, microdissected smooth muscle. At the protein level smoothelin was investigated by standard and quantitative immunohistochemistry.
The bladder muscularis expressed vascular and visceral smoothelin isoforms, and 2 of the known splice variants. In the smooth muscle of patients with detrusor instability and sensory urge a significant 2.4 and 2.2-fold increase, respectively, in smoothelin variant 1 mRNA was observed in comparison to that of normal controls. Analyses at the smoothelin protein level confirmed significant up-regulation in these bladder dysfunctions by a factor of 2.3 and 1.8, respectively. No significant difference in smoothelin expression was observed between detrusor instability and sensory urge.
Increased expression of smoothelin in patients with detrusor instability and sensory urge implies that the etiology of these dysfunctions includes changes in myogenic parameters. In addition, our data support the new classification of the International Continence Society for overactive bladder proposing that sensory urge and detrusor instability represent a single clinical entity.
我们确定了收缩性平滑肌细胞的标志物蛋白平滑肌肌动蛋白在人逼尿肌中的表达模式，并研究了其对膀胱过度活动症的可能影响。
获取13例膀胱过度活动症（感觉性尿急和逼尿肌不稳定）患者在注射肉毒杆菌毒素前的逼尿肌样本，并与8例在根治性膀胱切除术中获取的正常收缩、无梗阻膀胱的样本进行比较。通过Northern印迹法、变异体特异性逆转录-聚合酶链反应以及对激光捕获显微切割的平滑肌进行定量逆转录-聚合酶链反应，研究平滑肌肌动蛋白mRNA的表达模式。在蛋白质水平，通过标准和定量免疫组织化学法研究平滑肌肌动蛋白。
膀胱肌层表达血管和平滑肌肌动蛋白亚型以及2种已知的剪接变异体。与正常对照组相比，在逼尿肌不稳定和感觉性尿急患者的平滑肌中，平滑肌肌动蛋白变异体1 mRNA分别显著增加2.4倍和2.2倍。平滑肌肌动蛋白蛋白质水平的分析证实，在这些膀胱功能障碍中分别有2.3倍和1.8倍的显著上调。在逼尿肌不稳定和感觉性尿急之间，平滑肌肌动蛋白表达未观察到显著差异。
逼尿肌不稳定和感觉性尿急患者中平滑肌肌动蛋白表达增加意味着这些功能障碍的病因包括肌源性参数的改变。此外，我们的数据支持国际尿控协会对膀胱过度活动症的新分类，即感觉性尿急和逼尿肌不稳定代表单一临床实体。
