Prostate inflammation increases collagen and voiding dysfunction

项目摘要/摘要 很少有兽医临床医生从事泌尿外科研究，尽管他们的工作对象是 自发性排尿功能障碍。申请者是唯一合格的候选人，拥有兽医的 了解动物模型，接触容易发生自发性排尿功能障碍的患者，以及基本的 很少有兽医接受过泌尿科研究培训。 该奖学金的目标是为申请者提供成为一名成功的兽医的培训。 病理学家和翻译研究员。培训计划通过构建研究性学习来实现这一目标 设计技能，在主要文献方面有很强的背景，精通基本的组织病理学和基础知识 兽医知识和临床技能。此外，培训计划还促进了关键的专业发展 通过熟练掌握实验室业务技能、指导、协作、沟通、 和仁慈精神。该计划包括申请者培训和进展的每个部分的具体活动 将由申请人的赞助商和论文委员会进行评估。 这项研究的重点是前列腺胶原蛋白的堆积，它与烦人的下尿液有关。 老年男性的肠道症状(LUT)。患有LUT的男性通常小便频率和紧迫感增加， 排尿困难、膀胱排空不全、尿流力下降和尿流障碍。 流，降低生活质量和医疗保健费用的症状。前列腺癌的发病机制 胶原蛋白在人类和犬类体内的蓄积尚不清楚，但炎症与胶原蛋白有关 积累。特别是，前列腺液中白细胞介素1-β(IL-1β)的丰度与下尿路感染有关。 男人。IL-1β是炎症反应的介质，IL-1β在前列腺癌中的表达可被调控 转基因小鼠。这项训练计划将使用这些基因工程小鼠来测试最重要的 假设前列腺癌IL-1β导致炎症、纤维化和排尿功能障碍。 威斯康星大学麦迪逊分校是进行这些研究的理想环境，因为它是家 美国国立卫生研究院指定的奥布莱恩良性泌尿系统研究卓越中心的成员之一，这是仅有的三个专注于 与前列腺相关的疾病。威斯康星大学麦迪逊·奥布莱恩中心提供无与伦比的啮齿动物排尿功能 测试核心设施、每两个月一次的演讲者以及众多的协作机会。这件事的发起人 Work，Vezina博士，也是NIDDK赞助的生殖泌尿系统开发的长期贡献者 分子解剖学项目(GUDMAP)，带来详细的分子图谱方面的专业知识，培训将是 需要完成研究目标并贯穿申请者的整个职业生涯。威斯康星大学麦迪逊分校也有一家兽医， 药房和医学院在同一校园，提供对临床相关物种的访问，独特 资源和进一步的合作。

Project Summary/Abstract Few veterinary clinicians pursue a career in urologic research despite working with patients that develop spontaneous voiding dysfunction. The applicant is a uniquely qualified candidate, having a veterinarian’s understanding of animal models, access to patients prone to spontaneous urinary dysfunction, and the basic urologic research training few veterinarians receive. The goal of this fellowship is to provide the applicant with training for a successful career as a veterinary pathologist and translational researcher. The training plan accomplishes this goal by building research study design skills, a strong background in the primary literature, proficiency in basic histopathology, and foundational veterinary knowledge and clinical skills. In addition, the training plan fosters key professional development opportunities by building proficiency in laboratory business skills, mentorship, collaboration, communication, and grantsmanship. The plan includes specific activities for each segment of the applicant’s training and progress will be evaluated by the applicant’s sponsor and thesis committee. The proposed research focuses on prostatic collagen accumulation, which is linked to bothersome lower urinary tract symptoms (LUTS) in aging men. Men with LUTS often have increased frequency and urgency to urinate, difficulty initiating urination, incomplete bladder emptying, decreased urine stream force, and interruption of stream, symptoms that decrease quality of life and for which health care is costly. Mechanisms for prostatic collagen accumulation in humans and canines remain unknown but inflammation has been linked to collagen accumulation. In particular, prostatic interleukin-1-beta (IL-1β) abundance has been correlated with LUTS in men. IL-1β is a mediator of inflammatory responses, and prostatic expression of IL-1β can be manipulated in genetically engineered mice. This training plan will use these genetically engineered mice to test the overarching hypothesis that prostatic IL-1β drives inflammation, fibrosis and voiding dysfunction. The University of Wisconsin-Madison is the ideal environment to conduct these studies because it is the home of an NIH-designated O’Brien Center for Excellence in Benign Urologic Research, one of only three focused on prostate-related disease. The UW-Madison O’Brien Center provides an unparalleled rodent urinary function testing core facility, bimonthly speakers, and numerous opportunities for collaboration. The sponsor of this work, Dr. Vezina, is also a longstanding contributor to the NIDDK-sponsored Genitourinary Development Molecular Anatomy Project (GUDMAP), bringing expertise on detailed molecular mapping, training that will be needed to complete the research aims and throughout the applicant’s career. UW-Madison also has a Veterinary, Pharmacy, and School of Medicine on the same campus, providing access to clinically relevant species, unique resources and further collaborations.