Urinary Biomarkers of Lower Urinary Traxct Symptoms (LUTS) in Men

描述（由申请人提供）：本项目的目标是汇集一个跨学科的研究人员团队，以测试尿液代谢和蛋白质组学生物标志物可以预测人类下尿路症状（LUTS）治疗反应的假设，并确定最合适的动物模型用于LUTS的机制研究。目前的数据与人类LUTS具有多种病因和多种表现的观点最为一致。LUTS的合理病因包括但不限于良性前列腺增生、前列腺和膀胱颈炎症、前列腺和膀胱颈平滑肌张力变化以及下尿路神经系统变化。理想情况下，LUTS的治疗将考虑疾病的不同表现，以实现对个体患者更快速有效的治疗。实现这一目标的障碍包括缺乏足够的生物标志物来对人类LUTS的不同表现进行分层，以及缺乏关于LUTS不同表现的机制研究的最合适的动物模型的清晰度。为了解决这些阻碍该领域取得进展的障碍，该项目将开展分为三个具体目标的实验。目的1将使用蛋白质组学和代谢组学方法鉴定人类LUTS的尿液生物标志物。目的2将确定与LUTS症状的有效治疗相关的生物标志物表达的变化。目的3将进行种间比较研究，以确定人类LUTS患者，细菌性前列腺炎小鼠和膀胱炎诱导的尿路梗阻小鼠之间的生物标志物相似性。预计这些目标的完成将确定可以将LUTS分层为不同疾病亚型的生物标志物，预测对治疗的反应，并确定最适合研究与不同LUTS亚型相关的潜在机制的动物模型。这些目标的完成还将创建一个知识基础，以支持一个更全面的跨学科项目，使用人类患者数据和来自具有不同泌尿道疾病表现的动物模型的数据来确定LUTS的根本原因。

DESCRIPTION (provided by applicant): The goal of this project is to bring together an interdisciplinary team of researchers to test the hypothesis that urine metabolic and proteomic biomarkers can predict the response to therapy for human lower urinary tract symptoms (LUTS) and identify the most appropriate animal models for mechanistic studies of LUTS. Current data are most consistent with the idea that human LUTS has multiple etiologies and multiple manifestations. Plausible etiologies for LUTS include, but are not limited to, benign prostatic hyperplasia, inflammation in the prostate and bladder neck, changes in smooth muscle tone in the prostate and bladder neck, and neurologic changes in the lower urinary tract. Ideally, treatment for LUTS would take into account the different manifestations of disease to achieve more rapid and effective therapy for individual patients. Barriers to achieving this goal include the lack of adequate biomarkers to stratify the different manifestations of human LUTS and a lack of clarity regarding the most appropriate animal models for mechanistic studies of the different manifestations of LUTS. To address these barriers to progress in the field, this project will conduct experiments organized into three Specific Aims. Aim 1 will identify urine biomarkers of human LUTS using proteomic and metabolomic approaches. Aim 2 will identify changes in biomarker expression that correlate with effective treatment of LUTS symptoms. Aim 3 will conduct interspecies comparative studies to identify biomarker similarities among human LUTS patients, mice with bacterial prostatitis, and mice with hormone-induced urinary obstruction. It is anticipated that completion of these Aims will identify biomarkers that can stratify LUTS into different disease sub-types, predict response to therapy, and identify animal models that are most appropriate for investigating the underlying mechanisms associated with different sub-types of LUTS. Completion of these Aims will also create a base of knowledge needed to support a more comprehensive interdisciplinary project to determine the underlying cause(s) of LUTS using human patient data and data from animal models with different manifestations of urinary tract disease.