Molecular and neuro-inflammatory biology of aging bladder in normal and disease states

项目总结 近50%的绝经后妇女患有尿路感染，超过25%的绝经后妇女患有尿路感染 更年期妇女经历沉重的下尿路症状(LUT)，包括尿急， 大小便失禁和尿痛。到2050年，全球将有近15亿人达到≥65岁， 我们必须确定这些疾病的病理生理基础，以便治疗和预防它们。解决这个问题 挑战将需要跨学科的方法。因此，这是一项建立跨学科的建议 良性泌尿外科研究中心主要研究“老化膀胱的分子和神经炎性生物学” 在正常和疾病状态下“。该中心的首要、长期目标是促进快速翻译 我们对老年膀胱慢性炎症的认识从临床前到临床的突破 临床环境。该中心将通过汇集一个跨学科的医生团队和 具有不同专业知识领域的科学家系统地研究推动慢性阻塞性肺疾病的标志物和机制 炎症及其对小鼠模型和人类患者的影响。团队包括练习 对感染、年龄相关免疫感兴趣的妇科医生和基础及转化型科学家 膀胱的功能障碍和神经生物学。科研项目提出，背后的罪魁祸首 许多复发的UTI和LUTS病例是膀胱粘膜的慢性神经炎性过程，可以 表现为囊性膀胱炎，特征是膀胱镜下可见隆起的淋巴细胞聚集体。这个 该项目有三个目标，以定义细胞、分子、免疫和神经生物学变化 在小鼠和人的老年膀胱中伴随感染和慢性炎症。该中心将包括 负责促进协同合作的行政核心，与现有的NIH- 赞助O‘Brien中心的泌尿外科疾病和泌尿外科培训计划，并监督教育 浓缩计划。该计划将安排外部演讲者访问华盛顿大学 与中心目标相关的研讨会。该计划还将启动授课和实用的暑期奖学金 高中生、大学生和医学生在妇科相关实验室的研究经验。一起， 该中心支持的研究和教育活动将使该团队增加对泌尿外科的兴趣 研究并在了解复发性尿路感染和下尿路感染的病理生理学方面取得实质性进展。

PROJECT SUMMARY Nearly 50% of post-menopausal women suffer from urinary tract infections (UTIs), and over 25% of post- menopausal women experience burdensome lower urinary tract symptoms (LUTS), including urinary urgency, incontinence, and painful urination. Given that nearly 1.5 billion people will be ≥65 years old worldwide by 2050, we must determine the pathophysiologic basis of these disorders so as to treat and prevent them. Solving this challenge will require an interdisciplinary approach. Thus, this is a proposal to establish an Interdisciplinary Research Center in Benign Urology focused on “Molecular and neuroinflammatory biology of aging bladder in normal and disease states”. The overarching, long-term goal of the Center is to catalyze the rapid translation of breakthroughs in our understanding of chronic inflammation in the aged bladder from the preclinical to the clinical setting. The Center will accomplish this by bringing together an interdisciplinary team of physicians and scientists with diverse areas of expertise to systematically investigate markers and mechanisms driving chronic inflammation and its effects in mouse models and in human patients. The team includes practicing urogynecologists and basic and translational scientists interested in infections, age-associated immune dysfunction, and neurobiology of the bladder. The scientific research project proposes that the culprit behind many recurrent UTI and LUTS cases is a chronic neuro-inflammatory process of the bladder mucosa that can present as cystitis cystica, characterized as aggregates of lymphocytes that appear raised on cystoscopy. The Project has three Aims to define the cellular, molecular, immunological, and neurobiological changes that accompany infection and chronic inflammation in the aged bladder in mice and humans. The Center will include an Administrative Core responsible for fostering synergistic collaborations, integrating with existing NIH- sponsored O'Brien Centers in Urological diseases and urology training programs, and overseeing an Educational Enrichment Program. This Program will arrange visits to Washington University by outside speakers to present seminars relevant to the goals of the Center. The Program will also initiate didactic and practical Summer Scholar Research Experiences in Urogynecology-relevant labs for high school, college, and medical students. Together, the research and educational activities supported by the Center will allow the Team to increase interest in urology research and make substantial inroads into understanding the pathophysiology of recurrent UTIs and LUTS.