Prostate inflammation increases collagen and voiding dysfunction

前列腺炎症增加胶原蛋白和排尿功能障碍

• 批准号: 10228063
• 负责人: Hannah Margaret Ruetten
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2023-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228063
• 关键词: Acute; Aging; Anatomy; Animal Model; Benign; Biological Assay; Bladder; Businesses; Canis familiaris; Cells; Chronic; Clinical; Clinical Research; Clinical Skills; Collaborations; Collagen; Collagen Fiber; Collagen Gene; Communication; Core Facility; Development; Disease; Doxycycline; Drug Targeting; Elderly; Environment; Event; Faculty; Fellowship; Fibrosis; Fostering; Foundations; Frequencies; Functional disorder; Future; Genetically Engineered Mouse; Genitourinary system; Goals; Gold; Healthcare; Hematoxylin and Eosin Staining Method; Histologic; Histopathology; Home; Human; Immune; Increased frequency of micturition; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukin-1 beta; Interruption; Knowledge; Laboratories; Lead; Link; Literature; Lymphocyte; Measures; Mediating; Mentorship; Methods; Modeling; Molecular; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Outcome; Outcome Study; Paper; Pathologic; Pathologist; Pathology; Pathway interactions; Patients; Pattern; Periodicity; Pharmaceutical Preparations; Pharmacy Schools; Phenotype; Positioning Attribute; Prostate; Prostatic; Publishing; Quality of life; Recovery; Relapse; Research; Research Design; Research Training; Resolution; Resources; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid Arthritis; Rodent; Rodent Model; Stains; Stream; Students; Techniques; Testing; Time; Training; Tumor-infiltrating immune cells; United States National Institutes of Health; Universities; Up-Regulation; Urinary Retention; Urination; Urine; Veterinarians; Water; Wisconsin; Work; career; clinically relevant; cost; density; experience; innovation; irritation; lower urinary tract symptoms; male; medical schools; men; mouse model; neutrophil; novel; overexpression; reduce symptoms; research study; response; skills; tenure track; translational scientist; urinary; urologic

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.

项目总结/摘要 很少有兽医临床医生追求泌尿学研究的职业生涯，尽管与患者一起工作， 自发性排尿功能障碍申请人是唯一合格的候选人，具有兽医的 了解动物模型，获得患者易发生自发性排尿功能障碍的基本情况， 很少有兽医接受泌尿学研究培训。 该奖学金的目的是为申请人提供培训，使其成为成功的兽医 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，在主要文献的强大背景，在基本组织病理学的熟练程度，和基础 兽医知识和临床技能。此外，培训计划还促进关键的专业发展 机会，通过建立熟练的实验室业务技能，指导，协作，沟通， 还有格兰比亚该计划包括申请人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。 拟议的研究集中在前列腺胶原蛋白的积累，这是与麻烦的下尿路 老年男性的尿路症状（LUTS）。患有LUTS的男性通常会增加排尿的频率和紧迫性， 排尿困难，膀胱排空不全，尿流力下降， 流，症状，降低生活质量和卫生保健是昂贵的。前列腺的机制 胶原蛋白在人类和犬类中的积累仍然未知，但炎症与胶原蛋白有关。 积累特别是，前列腺白细胞介素-1-β（IL-1β）丰度与LUTS相关， 男人IL-1β是炎症反应的介质，并且IL-1β的前列腺表达可以在炎症反应中被操纵。 基因工程小鼠这项训练计划将使用这些基因工程小鼠来测试 前列腺IL-1β驱动炎症、纤维化和排尿功能障碍的假说。 威斯康星大学麦迪逊分校是进行这些研究的理想环境，因为它是家庭 美国国立卫生研究院指定的奥布莱恩良性泌尿学研究卓越中心，只有三个专注于 前列腺相关疾病威斯康星大学麦迪逊分校奥布莱恩中心提供了一个无与伦比的啮齿动物泌尿功能 测试核心设施，双月演讲者，以及众多的合作机会。的申办者 Vezina博士也是NIDDK赞助的泌尿生殖系统发展的长期贡献者 分子解剖学项目（GUDMAP），带来了详细的分子图谱的专业知识，培训，将是 需要完成研究目标和整个申请人的职业生涯。威斯康星大学麦迪逊分校也有一个兽医， 药学院和医学院在同一个校园，提供临床相关物种，独特的 资源和进一步合作。