John Hubert, Walch Michael, Lehmann Theresa, Maake Caroline
Department of Urology, Hirslanden Hospital, Zurich 8032, Switzerland.
World J Urol. 2009 Jun;27(3):411-8. doi: 10.1007/s00345-008-0365-x. Epub 2009 Jan 15.
Patients with benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) frequently develop lower urinary tract symptoms (LUTS). To elucidate the underlying pathomechanisms we focused on altered cellular communication between detrusor cells.
Bladder biopsies were collected from eight BPH patients with compensated BOO and from eight non-obstructed patients. Detrusor areas were separated by laser capture microdissection microscopy, and extracted RNA was subjected to quantitative RT-PCR for connexin43 and connexin45. Furthermore, localization of connexin45 and lysosome membrane associated protein 1 was studied by immunohistochemistry.
We found the human detrusor to express connexin45 rather than connexin43. Compared to controls, connexin45 expression was not significantly changed in detrusors of obstructed patients. However, connexin45 protein patterns were focally altered in obstruction.
Our study is the first to provide evidence that connexin45-coupling of detrusor cells may be regionally impaired in patients with BOO due to BPH. The altered connexin45 coupling may contribute to LUTS.
良性前列腺增生(BPH)和膀胱出口梗阻(BOO)患者常出现下尿路症状(LUTS)。为阐明其潜在的发病机制,我们聚焦于逼尿肌细胞间改变的细胞通讯。
从8例代偿性BOO的BPH患者和8例非梗阻患者中采集膀胱活检组织。通过激光捕获显微切割显微镜分离逼尿肌区域,提取的RNA进行连接蛋白43和连接蛋白45的定量逆转录聚合酶链反应。此外,通过免疫组织化学研究连接蛋白45和溶酶体膜相关蛋白1的定位。
我们发现人类逼尿肌表达连接蛋白45而非连接蛋白43。与对照组相比,梗阻患者逼尿肌中连接蛋白45的表达无显著变化。然而,连接蛋白45的蛋白模式在梗阻时局部改变。
我们的研究首次提供证据表明,由于BPH导致BOO的患者中,逼尿肌细胞的连接蛋白45偶联可能在局部受损。连接蛋白45偶联的改变可能导致LUTS。