Bladder Wall Remodeling in LUTS

描述（由申请人提供）：乔治M。宾夕法尼亚大学奥布莱恩泌尿学研究中心题为“下尿路症状中的膀胱壁重塑”，有三个关键要素：（1）五名主要研究者和联合PI的实验室，他们带来了分子生物学、细胞生物学、神经科学、生物化学、生理学、药理学和病理学方面的专业知识;（2）一个行政核心（核心A），提供行政和财政监督，对单个项目的研究进行质量控制，并协调中心的研究和互动;（3）膀胱组织核心（核心B），用作来自兔、大鼠和小鼠的LUTS的平滑肌组织的来源（正常和阻塞的膀胱和尿道）。此外，我们有教育和丰富和试点和可行性（P&F）计划，以吸引年轻的研究人员和建立在其他生物医学领域的研究人员进行泌尿学研究。这四个项目是：（1）社会压力引起的排尿功能障碍：Rita J. Valentino的排尿功能障碍模型;（2）Pamela S.霍华德（与纽约大学孙东田博士合作）;（3）梗阻诱导逼尿肌重塑的机制：缺氧和牵张的作用，来自Samuel K. Chacko;（4）细胞外基质改变对阻塞的反应，来自Edward J. Macarak。这两个P&F项目是：（1）雌激素对雌性家兔尿道功能的影响;（2）PBOO和雌激素对雌兔逼尿肌平滑肌的影响。诺辛顿O的焦点？Brien计划旨在阐明社会压力和PBOO诱导的膀胱壁功能和结构变化导致LUTS的机制。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排尿功能障碍的分子基础。更好地了解LUTS中膀胱壁和尿道的结构和功能改变的基本机制将有助于开发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.