Univ of Maryland Baltimore Interdisciplinary Research Center in Benign Urology

描述（由申请人提供）：OAB的病理生理尚不清楚。虽然目前提出的病因包括逼尿肌平滑肌和神经机制，但膀胱尿路上皮细胞（BUC）对OAB的潜在贡献是一种新的研究途径。马里兰大学良性泌尿学跨学科研究中心（UM-IRC）将进行一项计划研究，在该研究中，将从无尿失禁和无排尿症状的受试者（对照组）和有OAB症状的受试者（急迫性尿失禁）中获得膀胱尿路上皮活检。从这些活组织检查中获得的原代BUC培养物将在项目主任（Chai）和两位联合首席研究员（Birder, Keay）的实验室中进行研究。因为这些实验室已经有了独立的资金，所以使用了UM-IRC的多重PI方法。实验室研究的目的是获得初步的实验室数据，然后可以帮助统计支持下一个OAB试验，使用实验室客观测量作为主要结果。将测量的BUC的三种表型是细胞内多胺的表达，紧密连接蛋白的表达，以及通过响应低渗透和化学刺激释放三磷酸腺苷（ATP）来测量的细胞机械敏感性。早期的初步数据表明，在OAB - BUC中，这三种表型都发生了改变。在此规划阶段，研究小组将与三个已从事膀胱尿路上皮生物学基础研究的实验室建立稳固的合作关系。在规划阶段，将使用一个咨询小组来管理UM-IRC。由于前两年最重要的因素是招募OAB和对照受试者接受膀胱尿路上皮活检，除了受试者的安全性外，咨询小组还将持续监测招募人数。UM-IRC将利用马里兰大学尿失禁和骨盆中心进行招募。目前正在进行的几项OAB临床试验可以帮助本提案的招募。根据区域研究基金的预算限制，将招收10名OAB和10名对照科目。UM-IRC将利用跨学科方法进行将尿路上皮病理生理学与OAB联系起来的转化研究。

DESCRIPTION (provided by applicant): The pathophysiology of OAB is unknown. While there are proposed etiologies including detrusor smooth muscle and neural mechanisms, the potential contribution of the bladder urothelial cells (BUC) to OAB is a new avenue of inquiry. The University of Maryland Interdisciplinary Research Center (UM-IRC) in benign urology will perform a planning study in which bladder urothelial biopsies will be obtained from subjects with no urinary incontinence and no voiding symptoms (controls) and from subjects with OAB symptoms (urge incontinence). Primary BUC cultures derived from these biopsies will be studied in the laboratories of the Program Director (Chai) and the two co-principal investigators (Birder, Keay). Because these labs already have independent funding, the multiple PI approach for the UM-IRC is utilized. The intent of the laboratory studies Is to obtain preliminary laboratory data which then can help statistically power the next OAB trial using laboratory objective measures as primary outcomes. The three phenotypes of BUC that will be measured are expression of intracellular polyamines, expression of tight junction proteins, and cellular mechanosensitivity measured by adenosine triphosphate (ATP) release in response to hypo-osmotic and chemical stimuli. Early preliminary data suggest alterations in all three of these phenotypes in OAB BUC. During this planning phase, the UM-IRC will firmly establish collaboration among the three laboratories which are already active in basic bladder urothelial biologic studies. An advisory panel will be used to govern the UM-IRC during the planning phase. Because the most important factor during the first two year is recruitment of OAB and control subjects to undergo bladder urothelial biopsies, the advisory panel will maintain constant surveillance of the recruitment numbers in addition to subject safety. The UM-IRC will utilize the Univ of Maryland Continence and Pelvic Center for recruitment. There are several OAB clinical trials currently ongoing which can help with the recruitment for this proposal. Based on the budgetary constraints of the RFA, 10 OAB and 10 control subjects will be enrolled. The UM-IRC will utilize an interdisciplinary approach in performing translational research linking urothelial pathophysiology to OAB. PUBLIC HEALTH RELEVANCE: Overactive bladder (OAB) is a highly prevalent condition affecting over 16 million people in the USA. Diagnosis and treatment for OAB remains rudimentary and rely almost exclusively on patient reported symptoms. By increasing the understanding of this condition with basic science experiments, we hope to understand the causes for OAB. Specifically we will focus on the role of the bladder lining cells (urothelial CRIIS) in the cause of OAB.