Bladder Wall Remodeling in LUTS

描述(由申请人提供):乔治·m·奥布莱恩泌尿外科研究中心在宾夕法尼亚大学的题为“在附近地区膀胱壁重建”有三个关键要素:(1)五个主要的实验室调查和Co-PIs带来专业知识分子生物学、细胞生物学、神经科学、生物化学、生理学、药理学、病理学;(2)行政核心（核心A）提供行政和财政监督，对个别项目的研究进行质量控制，并协调中心的研究和互动；(3)膀胱组织核（Core B），作为兔、大鼠和小鼠（正常和阻塞的膀胱和尿道）LUTS平滑肌组织的资源。此外，我们有教育和丰富和试点和可行性（P&F）计划，以吸引年轻的研究者和在其他生物医学领域工作的成熟的研究者到泌尿学研究。这四个项目分别是：(1)Rita J. Valentino的社会压力性尿功能障碍：功能障碍排尿模型；(2) Pamela S. Howard（与纽约大学孙东天博士合作）对尿路上皮结构改变后膀胱壁重塑的研究；(3)阻塞致逼尿肌重构的机制：缺氧和拉伸的作用（Samuel K. Chacko）；(4)细胞外基质对阻塞的响应。两个P&F项目分别是：(1)女性尿道功能：雌激素的作用（张少华）；(2) PBOO和雌激素对Gina M. Northington家兔逼尿肌平滑肌的影响。O？Brien程序阐明社会压力的机制——PBOO-induced膀胱壁功能和结构变化导致附近地区。这些研究将为儿童排尿功能障碍提供一个有用的模型，并阐明绝经期妇女和老年男性bph诱导的PBOO尿功能障碍的分子基础。更好地了解LUTS患者膀胱壁和尿道结构和功能改变的基本机制将有助于制定针对导致下尿路功能改变的分子事件的治疗策略。

DESCRIPTION (provided by applicant): The George M. O'Brien Urology Research Center at the University of Pennsylvania entitled "Bladder Wall Remodeling in LUTS" has three key elements: (1) the laboratories of five principal investigators and the Co-PIs that bring expertise in molecular biology, cellular biology, neuroscience, biochemistry, physiology, pharmacology, and pathology; (2) an Administrative Core (Core A) to provide administrative and fiscal oversight, quality control for the research within individual projects and coordination of the research and interactions in the Center; (3) a Bladder Tissue Core (Core B) to serve as a resource for smooth muscle tissue of the LUTS from rabbits, rats, and mice (normal and obstructed bladders and urethra). In addition, we have Educational and Enrichment and Pilot and Feasibility (P&F) programs to attract young investigators and established investigators in working in other biomedical areas to urologic research. The four projects are: (1) Social-stress-induced urinary dysfunction: A model of dysfunctional voiding from Rita J. Valentino; (2) Bladder wall remodeling following alteration of urothelial structure from Pamela S. Howard (in collaboration with Dr. Tung-Tien Sun of NYU); (3) Mechanism for obstruction-induced detrusor remodeling: role of hypoxia and stretch from Samuel K. Chacko; and (4) Extracellular matrix changes response to obstruction from Edward J. Macarak. The two P&F projects are: (1) Urethral function in females: A Role for estrogen from Shaohua Chang; and (2) The effect of PBOO and estrogen on detrusor smooth muscle in female rabbits from Gina M. Northington. The focus of the O?Brien Program is to elucidate the mechanism for social stress- and PBOO-induced functional and structural changes in the bladder wall leading to LUTS. These studies will provide a useful model for dysfunctional voiding in children and elucidate the molecular basis for urinary dysfunction in menopausal women and aging men with BPH-induced PBOO. A better understanding of the basic mechanisms for alteration of the structure and function of the bladder wall and urethra in LUTS would help to develop therapeutic strategies targeting altered molecular events that cause altered function in lower urinary tract.